The document discusses immuno-oncology and the relationship between cancer and the immune system. It provides an overview of topics that will be covered in an upcoming webinar, including advances in immuno-oncology for different cancer types and combination immunotherapy approaches. The document then reviews key topics in more depth, including how immuno-oncology focuses on improving the body's immune response against cancer and recent immunotherapy approvals. It also discusses how cancer can evade the immune system and strategies for cancer immunotherapy, such as manipulating co-stimulatory signals, enhancing antigen presenting cells, and using cytokines, monoclonal antibodies, and cancer vaccines.
IMMUNE RESPONSE TO TUMORS-Humoral immunity
-Cellular Immunity- Failure of Host Defenses
- Evasion of Immune Responses by Tumors
- Cancer Immunosurveillance vs Immunoediting- Immunotherapy
IMMUNE RESPONSE TO TUMORS-Humoral immunity
-Cellular Immunity- Failure of Host Defenses
- Evasion of Immune Responses by Tumors
- Cancer Immunosurveillance vs Immunoediting- Immunotherapy
The presentation outlines aspects of immunity against cancer, evasion strategies by cells, immunotherapy in cancer, cancer vaccines etc. Download and view the slideshow for better experience.
Prepared in Sept 2014
Altering the specificity of T cell receptor (TCR) is one of the popular strategies to genetically modify T cells to enhance the tumor-killing activity of T cells. From a tumor-reactive T cell or active anti-tumor T-cell antigens, the appropriate target sequence is introduced to modify T cells to target a broad range of tumors with improved specificity. https://www.creative-biolabs.com/car-t/cellrapeutics-tcr-technology.htm
T-Cell Activation
• Concept of immune response
• T cell-mediated immune response
• B cell-mediated immune response
I. Concept of immune response
• A collective and coordinated response to the introduction of foreign substances in an individual mediated by the cells and molecules in the immune system.
II. T cell-mediated immune response
• Cell-mediated immunity is the arm of the adaptive immune response whose role is to combat infection of intracellular pathogens, such as intracellular bacteria (mycobacteria, listeria monocytogens), viruses, protozoa, etc.
The presentation outlines aspects of immunity against cancer, evasion strategies by cells, immunotherapy in cancer, cancer vaccines etc. Download and view the slideshow for better experience.
Prepared in Sept 2014
Altering the specificity of T cell receptor (TCR) is one of the popular strategies to genetically modify T cells to enhance the tumor-killing activity of T cells. From a tumor-reactive T cell or active anti-tumor T-cell antigens, the appropriate target sequence is introduced to modify T cells to target a broad range of tumors with improved specificity. https://www.creative-biolabs.com/car-t/cellrapeutics-tcr-technology.htm
T-Cell Activation
• Concept of immune response
• T cell-mediated immune response
• B cell-mediated immune response
I. Concept of immune response
• A collective and coordinated response to the introduction of foreign substances in an individual mediated by the cells and molecules in the immune system.
II. T cell-mediated immune response
• Cell-mediated immunity is the arm of the adaptive immune response whose role is to combat infection of intracellular pathogens, such as intracellular bacteria (mycobacteria, listeria monocytogens), viruses, protozoa, etc.
Drought refers to a prolonged period of abnormally low rainfall, leading to a shortage of water. A drought can last for several months or years. Sometimes, droughts are declared for a full district for a few years.
It can have a substantial impact on the ecosystem and agriculture of the affected region and harm to the local life and economy. This module highlights the basics of climatic drought.
Climate data can provide a great deal of information about the atmospheric environment that impacts almost all aspects of human endeavour. This module explains the importance of climate data, its storage, security, applications and other aspects, in a nutshell.
Weather forecasting is the prediction of the state of the atmosphere for a given location using the application of science and technology. This includes temperature, rain, cloudiness, wind speed, and humidity. Weather warnings are a special kind of short-range forecast carried out for the protection of human life. This module explains the details of weather forecasting.
Meteorological observations are made for a variety of reasons. They are used for the real-time preparation of weather charts and maps, for weather forecasts and severe weather warnings, for the study of climate, and for local weather-dependent operations. This module highlights all related details.
Adaptation to global change must include prudent management of groundwater as a renewable, but slow-feedback resource in most cases. Groundwater storage is already over-tapped in many regions, yet available subsurface storage may be a key to meeting the combined demands of agriculture, industry, municipal and domestic water supply, and ecosystems during times of shortage.
Climate change is both a development issue and an environmental issue. Developing countries are more vulnerable to climate change than rich countries. CC may be limited to a specific region, or it may occur across the whole Earth.
It can be caused by recurring and cyclical climate patterns.
The causes of climate change are many. There is a need to understand these factors for reducing the effects.
The Earth’s climate is changing. Temperatures are rising, snow and rainfall patterns are shifting, and more extreme climate events—like heavy rainstorms and record-high temperatures, are already taking place. One important way to track and communicate the causes and effects of climate change is
through the use of indicators. An indicator represents the state or trend of certain environmental or societal conditions over a given area and a specified period of time. This lesson highlights all those indicators for a better understanding of climate change.
Map is a drawn or printed representation of the physical features of the Earth.
It is the best tool to show, understand and analyse the features of an area. Cartography is the art and science of making maps. This module highlights many information on maps, types and their uses.
To aid in understanding many complex interactions, scientists often build mathematical models that represent simple climate systems. This module highlights the fundamentals of climate models.
Research is a systematic inquiry to describe, explain, predict and control the observed phenomenon. Research is a structured inquiry that utilizes acceptable scientific methodology to solve problems and create new knowledge that is generally applicable.
The climate of a region is ultimately determined by the radiation energy of the sun, and its distribution and temporal fluctuations. The long-term state of the atmosphere is a function of a variety of interacting elements. They are: Solar radiation, Air masses, Pressure systems (and cyclone belts),Ocean Currents, and topography.
The term precipitation is also used to refer all forms of falling moisture viz., rainfall, snowfall, sleet, hail etc. Rainfall occurs in the form of a pattern. Atmospheric Precipitation is a wonderful process for the whole globe to use. This module explains it in general.
The density and distribution of climatological stations to be established in a land network within a given area depend on the meteorological elements to be observed, the topography and land use in the area, and the requirements for information about the specific climatic elements concerned. This module highlights all these aspects.
Atmospheric ozone protects the Earth and its inhabitants from the harmful ultraviolet radiation of the Sun. Without this protective layer, more ultraviolet radiation would reach the surface of the Earth and cause damage to plant, animal and human life. This module explains the importance of ozone, the causes of its depletion and the effects expected on earth's systems.
Dr. ihsan edan abdulkareem alsaimary
PROFESSOR IN MEDICAL MICROBIOLOGY AND MOLECULAR IMMUNOLOGY
ihsanalsaimary@gmail.com
mobile : 009647801410838
university of basrah - college of medicine - basrah -IRAQ
Patients are beginning to benefit from antibody based, cellular and vaccine approaches that are effective against genetically diverse and therapy-resistance cancers.
A presentation descripes tumors,pathogensis,devlopment,antigenes and genes.
how host responds to them and how tumors evade immunity with latest lines of therapy and prevention.
facaulity of pharmacy.Damascus university.master of libaratory diagnossis. immunology.
Baraa ALomar and feras deban
ROLE OF IMMUNE CELLS IN CANCER AND TARGETING IMMUNE CELLS FOR CANCER THERAPYSIVASWAROOP YARASI
Cancer immunotherapy is a therapy used to treat cancer patients that involves or uses components of the immune system. Some cancer immunotherapies consist of antibodies that bind to, and inhibit the function of, proteins expressed by cancer cells. Other cancer immunotherapies include vaccines and T cell infusions.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
2. Webinar topics ahead
1. Review of immuno-oncology
2. Advances in immuno-oncology
3. Immuno-oncology: understanding function & dysfunction of the immune
system in cancer
4. Melanoma as a model tumour for immuno-oncology
5. Recent immunotherapy advances changing standard of care in
metastatic melanoma
6. Evolving role of immunotherapy in prostate cancer
7. What future opportunities may immuno-oncology provide for improving
the treatment of patients with lung cancer?
8. Emerging immunotherapies for renal cell carcinoma
9. Combination immunotherapy approaches
10. Evolution of end points for cancer immunotherapy trials
11. Can immuno-oncology offer a truly pan-tumour approach to therapy?
3. A look-ahead
• Immuno-oncology
• Tumors and Metastasis
• Oncogenes and Cancer Induction
• Tumor Antigens
• Tumors and the Immune Response
• Immunotherapy
4. Immuno-oncology
• Immuno-oncology is a new area of medicine
that focuses on the development and
delivery of therapies that improve the body's
intrinsic potential for generating an effective
immune response against cancer.
• Although immuno-oncology is still in its
infancy, immunotherapy has been yielding
clinical results for some time, and the most
recent agents entering the clinic look even
more promising.
5. Immuno-oncology
• In April 2010, sipuleucel-T became the first
therapeutic vaccine to be approved by US
FDA for the therapy of prostate cancer.
– Subsequently, in 2011, ipilimumab, a fully human
monoclonal antibody which blocks cytotoxic T-
lymphocyte-associated antigen-4, became the first
agent approved in the EU for the treatment of
adult patients with unresectable or metastatic
melanoma who have received prior therapy that
showed an overall survival benefit in a randomised
phase III trial.
6. Immuno-oncology
• Hence, many think that immunotherapy
should be considered alongside
1. Surgery,
2. Chemotherapy and
3. Radiotherapy
4. As the 4th
cornerstone of anticancer treatment.
• Influencing the body’s immune system to give
an immune response against cancer is
immuno-oncology's primary focus.
8. Cancer
“altered self-cells that have escaped normal
growth regulation mechanisms”
neoplasm: tumor
benign vs. malignant
metastasis: spreading of cancerous cells via
blood or lymph to various tissues
11. What makes cancer
“cancer”?
1. decreased requirements for growth
factors and serum
2. are no longer anchorage dependent
3. grow independently of density
normal cells:
eventually enter Go
confluent monolayer CHECKPOINT FAILURE
contact inhibition
12. Malignant Transformation
• are like in vitro cancers
• two phases
1.initiation (changes in genome)
2.promotion (proliferation)
13. Malignant Transformation
• chemical and physical carcinogens
• virally induced transformation
• cultured tumors: good models for study
• cancer cells are basically immortal
15. What can go right?
• induction of cellular
proliferation
• inhibition of cellular
proliferation, a.k.a. tumor-
suppressor genes
• regulation of programmed
cell death
16. What can go wrong?
• chromosomal translocations
• tandem repeats: HSRs
• mutations in proto-oncogenes
• viral integration
• growth factors and their receptors
20. Tumors of the Immune System
• Lymphomas
– Solid tumors w/in lymphoid tissue (bone marrow,
lymph nodes, thymus)
– Hodgkin’s & non-Hodgkin’s
• http://www.lymphomainfo.net/
• Leukemias
– Proliferate as single cells
– Acute or Chronic depending on the progression of
disease
• Acute- appear suddenly and progress rapidly;
arise is less mature cells (ie ALL, AML)
• Chronic- much less aggressive and develop
slowly; mature cells (ie CLL and CML)
22. TSTAs
• Unique to tumor cells
• DO NOT occur on normal cells in the body
• Novel proteins created my mutation presented
on class I MHC
• Can either be chemically/physically induced or
virally induced tumor antigens
23. Chemically/Physically Induced
• Specific Immunologic Response that can
• Protect against later challenge by live cells
• Of the same line but not other tumor-line Cells.
• Methylcholanthrene / UV light
24. Virally Induced
• Express tumor antigens shared by all tumors induced
by the same virus
• Burkitt’s Lymphoma
– Epstein Barr
• HPV
25. TATAs
• NOT unique to tumor cells
• DO occur on normal cells in the body
• So where’s the problem?
– Fetal/adult presence
– Concentration of Growth Factors and Growth
Factor Receptors
26. TATAs cont’d
• Oncofetal Tumor Antigens (AFP & CEA)
– Normally appear in fetus before
immunocompetence
– Later recognized as non-self
• Oncogene Proteins
• Human Melanomas
27. Virally Induced Tumors
• Virally induced tumors have the same
antigens for each tumor caused by that
virus.
• HPV
28. Immune Response to Tumors
• Mostly a cell-mediated
response
• NK Cells
– Not MHC restricted
– Fc receptor binds to antibody
coated tumor cell ADCC
– Chedieak-Higashi syndrome
• Macrophages
– Not MHC restricted
– Elicits ADCC
– TNF-alpha
• Immune Surveillance Theory
29. So, you have a tumor cell. Now
what?
• You need three things:
1. “See” the cancer
• Ternary complex and costimulation by B7
1. Activate lymphocytes
• Release IL-2, IFN-gamma, and TNF-alpha
1. Cancer cells must be susceptible to killing
• CTL lysis, macrophages, NK cells
Info From:
http://www.brown.edu/Courses/Bio_160/Projects1999/cancer/imevstca.html#Introduction
30. But if the body has all
these defenses, why do so
many people still have
cancer?
31. Conniving Cancer
• Bad antibodies?
– Some antibodies do not protect against tumor growth,
but also ENHANCE it.
– Release of immunosuppressive cytokines
• transforming growth factor-beta (TGF-beta), interleukin-10
(IL-10) and vascular endothelial growth factor (VEGF)
• Hide and go Seeking Antigen
– Antigens actually seem to “hide” in the presence of
antibody
– Also, some cancer cells completely shed themselves
of the antigen
32. Effect TGF-beta IL-10 VEGF
Inhibition of T-cell growth
+ - +
Inhibition of CTL differentiation
+ + +
Inhibition of cytokine production
+ + -
Induction of T-cell anergy
+ - -
Downregulation of cytotoxic potential
+ + -
Inhibition of antigen presentation
+ + -
Shift in the Th1-Th2 balance towards
Th2
+ + -
Downregulation of
adhesion/costimulatory molecules
+ + -
Resistance to CTL-mediated lysis
- + -
Source: Chouaib et al 1997
34. And the final blow…
• Lack of Co-
Stimulatory
Signal
35.
36.
37. Cancer Immunotherapy
• Manipulation of Co-Stimulatory Signal
• Enhancement of APC Activity
• Cytokine Therapy
• Monoclonal Antibodies
• Cancer Vaccines
38. Manipulation of Co-Stimulatory
Signal
• Tumor immunity can be enhanced by providing the
co-stimulatory signal necessary for activation of CTL
precursors (CTL-Ps)
• Fig. 22.11a
40. Enhancement of APC Activity
• GM-CSF (Granulocyte-macrophage colony-
stimulating factor)
remember: CSFs are cytokines that induce the
formation of distinct hematopoietic cell lines
• Fig 22.11b
41. Cytokine Therapy
• Use of recombinant cytokines (singly or in
combination) to augment an immune
response against cancer
– Via isolation and cloning of various cytokine
genes such as:
– IFN-α, β, and γ
– Interleukin 1, 2, 4, 5, and 12
– GM-CSF and Tumor necrosis factor (TNF)
42. Cytokine Therapy Cont.
I. Interferons
• Most clinical trials involve IFN-α
• Has been shown to induce tumor regression in
hematologic malignancies i.e. leukemias,
lymphomas, melanomas and breast cancer
• All types of IFN increase MHC I expression
• IFN-γ also has also been shown to increase
MHC
II expressionon macrophages and increase
activity of Tc cells, macrophages, and NKs
43. Cytokine Therapy Cont.
II. Tumor Necrosis Factors
• Kills some tumor cells
• Reduces proliferation of tumor cells without
affecting normal cells
How?
• Hemorrhagic necrosis and regression, inhibits
tumor induced vascularization (angio-genesis)
by damaging vascular endothelium
44. Cytokine Therapy Cont.
III. In Vitro-Activited LAK & TIL cells
A. Lymphocytes are activated against
tumor
antigens in vitro
• Cultured with x-irradiated tumor cells
in
presence of IL-2
• Generated lymphokine activated
killer
cells (LAKs), which kill tumor cells
without affecting normal cells
45. In Vitro-Activated LAK and TIF cells Cont.
B. Tumors contain lymphocytes that have
infiltrated tumor and act in anti-tumor
response
• via biopsy, obtained cells and
expanded population in vitro with
• generated tumor-infiltrating lympho-
cytes (TILs)
