Anti-TNF in Melanoma Immunotherapy
34 Questions
1 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to Lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is the primary role of Tumor Necrosis Factor (TNF) in cancer?

  • Only causes cancer cell death
  • Has a dual role, inducing both cell death and promoting tumor growth (correct)
  • Inhibits immune response
  • Only promotes tumor growth

TNF has been solely associated with increasing tumor progression without any benefits.

False (B)

Who is the professor associated with the research on ANTI-TNF in melanoma immunotherapy?

Bruno Ségui

The clinical trial TICIMEL focuses on advanced melanoma patients and is classified as a phase _____ trial.

<p>1b</p> Signup and view all the answers

Match the following terms with their corresponding roles in melanoma treatment:

<p>TNF = Induces cell death MELANFa = Preclinical research program TICIMEL = Phase 1b clinical trial Anti-TNF therapy = Potentially reduces tumor progression</p> Signup and view all the answers

What is one of the functions of TNF in the context of cancer?

<p>Enhances dendritic cell maturation (B)</p> Signup and view all the answers

Chronic inflammation is associated with tumor progression and metastasis.

<p>True (A)</p> Signup and view all the answers

What does MDSC stand for in the context of immunosuppression?

<p>Myeloid-Derived Suppressor Cells</p> Signup and view all the answers

TNF has pleiotropic functions in anti-cancer immune response, including in __________.

<p>melanoma</p> Signup and view all the answers

Match the following cancer-related factors with their effects:

<p>TNF = Proliferation and differentiation Chronic inflammation = Angiogenesis Endothelial cell death = Leukocyte infiltration/activity Dendritic cells = Co-stimulation</p> Signup and view all the answers

Which of the following is NOT a function of TNF related to cancer cells?

<p>Promoting apoptosis in all cell types (A)</p> Signup and view all the answers

Lymphocyte-mediated cytotoxicity is unrelated to TNF's function in anti-cancer immune response.

<p>False (B)</p> Signup and view all the answers

The process of __________ involves the migration of leukocytes into tumors.

<p>infiltration</p> Signup and view all the answers

What type of molecules are involved in Treg and Breg adhesion as referenced in the JCI 2012?

<p>Adhesion molecules (B)</p> Signup and view all the answers

Ipilimumab is used as a monotherapy in melanoma immunotherapy.

<p>False (B)</p> Signup and view all the answers

What percentage of patients experienced complete response when treated with the combined immune checkpoint inhibitor?

<p>22%</p> Signup and view all the answers

The anti-cancer immune response in melanoma includes the expression of ______ which interacts with immune checkpoints.

<p>PD-L1</p> Signup and view all the answers

Match the following terms with their appropriate descriptions:

<p>Ipilimumab = Anti CTLA-4 Ab Nivolumab = Anti PD-L1 Ab CD73 = Involved in immune suppression TNF = A cytokine involved in inflammation</p> Signup and view all the answers

What type of adverse events are most commonly seen in patients receiving immune checkpoint inhibitors?

<p>Immune-related adverse events (D)</p> Signup and view all the answers

Melanoma dedifferentiation involves the gain of melanocytic antigens.

<p>False (B)</p> Signup and view all the answers

What is the role of anti-TNF therapy in patients with colitis caused by immunotherapy?

<p>Corticotherapy ± anti-TNF (infliximab) is used to manage adverse effects.</p> Signup and view all the answers

What is the role of TNF blockade in mouse melanoma models?

<p>Inhibits melanoma growth (B)</p> Signup and view all the answers

Anti-TNF therapy enhances anti-PD-1 therapy effectiveness against B16K1 melanoma.

<p>True (A)</p> Signup and view all the answers

What type of mice were used in the melanoma experiments?

<p>C57BL/6 WT mice</p> Signup and view all the answers

Etanercept is a drug that blocks _____ in melanoma treatment.

<p>TNF</p> Signup and view all the answers

Match the treatment with its effect:

<p>Etanercept = Blocks TNF Anti-PD-1 = Increases survival CD8+ TILs = Enhances immune response TNF = Promotes melanoma growth</p> Signup and view all the answers

What was the primary effect measured in the studies involving Etanercept?

<p>Tumor volume (B)</p> Signup and view all the answers

The experiments utilized both WT mice and CD8 KO mice.

<p>True (A)</p> Signup and view all the answers

What does TILs stand for?

<p>Tumor Infiltrating Lymphocytes</p> Signup and view all the answers

The main immune cells measured in response to melanoma treatments were _____ T cells.

<p>CD8+</p> Signup and view all the answers

The experiments confirmed that TNF facilitates melanoma growth by enhancing CD8 T cells.

<p>False (B)</p> Signup and view all the answers

What does the abbreviation 'WT' stand for in the context of the mice used?

<p>Wild Type</p> Signup and view all the answers

The immune response was assessed at _____ days in the study.

<p>12</p> Signup and view all the answers

Which of the following is NOT a focus of the studies involving TNF blockade?

<p>Improvement in bone density (C)</p> Signup and view all the answers

Flashcards

TNF's Dual Role in Cancer

Tumor Necrosis Factor (TNF) is a powerful protein that can either kill cancer cells or contribute to tumor growth.

TNF's Cancer-Killing Effect

TNF was first discovered for its ability to kill cancer cells in laboratory experiments.

TNF's Tumor-Promoting Effect

TNF can also promote blood vessel growth in tumors, thereby enhancing tumor growth and metastasis.

TNF: A Multifaceted Cytokine

TNF is a complex molecule involved in various cellular processes, including inflammation, immune responses, and cell death.

Signup and view all the flashcards

TNF's Complexity in Cancer Treatment

TNF's dual role in cancer highlights the complexity of cancer biology and the need for targeted therapies to specifically exploit its beneficial effects while minimizing its undesirable effects.

Signup and view all the flashcards

Adhesion molecule

A molecule on the surface of a cell that helps it adhere to other cells, such as immune cells.

Signup and view all the flashcards

Regulatory T cell (Treg)

A type of white blood cell that helps to suppress the immune system and prevent autoimmune reactions.

Signup and view all the flashcards

Breg

A type of T cell that suppresses inflammation and helps to maintain immune tolerance.

Signup and view all the flashcards

Tumor Necrosis Factor (TNF)

A protein that plays a role in immune responses and can trigger inflammation.

Signup and view all the flashcards

Melanoma dedifferentiation

The loss of the characteristic features of a melanoma cell, which can make it more difficult to target with immunotherapy.

Signup and view all the flashcards

PD-L1

A protein on the surface of cancer cells that interacts with immune cells to suppress the anticancer immune response.

Signup and view all the flashcards

CD73

An enzyme expressed on the surface of some immune cells that can help to suppress the anticancer immune response.

Signup and view all the flashcards

Cancer immunotherapy

The use of the immune system to fight cancer, often utilizing immune checkpoint inhibitors.

Signup and view all the flashcards

What is TNF?

Tumor Necrosis Factor (TNF) is a powerful molecule that can kill cancer cells and regulate various aspects of tumor growth and spread.

Signup and view all the flashcards

How does TNF kill cancer cells?

TNF can attack cancer cells directly, leading to their death. This is a key way TNF helps control tumor growth.

Signup and view all the flashcards

How does TNF influence cancer cell behavior?

TNF influences various aspects of cancer development, including how quickly cancer cells divide, move, differentiate, and become resistant to treatments.

Signup and view all the flashcards

How is TNF involved in the tumor microenvironment?

TNF plays a crucial role in the tumor microenvironment, the area surrounding the tumor. It affects inflammation, new blood vessel growth, and the makeup of the surrounding tissue, impacting tumor growth and spread.

Signup and view all the flashcards

How does TNF support the immune response to cancer?

TNF helps create a supportive environment for the immune system to fight cancer. It activates immune cells like dendritic cells, helps them mature, and boosts their ability to fight cancer.

Signup and view all the flashcards

How does TNF regulate the immune response?

TNF can induce apoptosis, a type of programmed cell death, in certain immune cells, like CD8 T cells, as a way to control the immune response and prevent excessive activation.

Signup and view all the flashcards

How does TNF suppress immunosuppressive cells?

Certain immune cells, called myeloid-derived suppressor cells (MDSCs), can be suppressed by TNF. This limits their ability to dampen the immune response against cancer.

Signup and view all the flashcards

What is the overall impact of TNF on cancer?

TNF plays a complex role in cancer, both promoting and inhibiting tumor growth. Understanding this duality is essential for developing effective cancer treatments.

Signup and view all the flashcards

Orthotopic Melanoma Model

A type of tumor growth where melanoma cells are injected directly into the skin of C57BL/6 mice, mimicking the natural progression of melanoma.

Signup and view all the flashcards

CD8+ Tumor Infiltrating Lymphocytes (TILs)

A type of immune cell that plays a critical role in killing tumor cells. CD8+ TILs are found in the tumor microenvironment.

Signup and view all the flashcards

Etanercept

A laboratory drug that blocks the activity of TNF. This is often used to study the effects of TNF on tumor growth and immune responses.

Signup and view all the flashcards

T-cell Immunoreceptor with Immunoglobulin and ITIM Domains (TIM-3)

A molecule on the surface of some immune cells that helps regulate and control the immune response. It is an immune checkpoint molecule.

Signup and view all the flashcards

Anti-PD-1 Therapy

A type of therapy that uses antibodies to block the PD-1 receptor on immune cells. This helps to reactivate the immune system to fight cancer.

Signup and view all the flashcards

Complete Responses

The ability of a treatment method to completely eliminate the disease.

Signup and view all the flashcards

Double Standard Treatment of Melanoma

A study involving a control group and a treatment group, where both groups receive a standard treatment for melanoma alongside additional experimental treatments.

Signup and view all the flashcards

Overall Survival (%)

A type of study that measures the time it takes for a specific outcome to occur, such as the time it takes for a tumor to grow or for a patient to die.

Signup and view all the flashcards

Percent Survival

The fraction of patients who are still alive at a specific point in time after the start of a study.

Signup and view all the flashcards

Treatment Groups

A study involving multiple different treatment groups, each receiving a different combination of therapies.

Signup and view all the flashcards

Mean Fluorescence Intensity (MFI)

A measure of the intensity of a signal detected on cells using a flow cytometer. It helps to understand the expression levels of certain molecules on cells.

Signup and view all the flashcards

Synergy

The combination of several factors or treatments that together lead to a better outcome than any single factor or treatment alone.

Signup and view all the flashcards

Study Notes

Anti-TNF in Melanoma Immunotherapy: From Basic Findings to the Clinic

  • TNF plays a dual role in cancer, including melanoma. It can induce both cancer cell death and tumor progression/metastasis.
  • TNF also influences tumor microenvironment, including chronic inflammation and changes in the tumor's stroma or blood vessels.
  • TNF plays a pleiotropic role in anti-cancer immune response, impacting dendritic cell maturation, co-stimulation, lymphocyte-mediated cytotoxicity, and adhesion molecules.

Immunosuppressive Function of TNF

  • TNF influences the immune response, including immunosuppressive roles in melanoma, such as with Myeloid-derived suppressor cells (MDSC), regulatory T cells (Treg), and Breg cells.
  • TNF also impacts melanoma dedifferentiation (loss of melanocyte antigens) and alters CD8 T cells to limit immune responses.
  • TNF contributes to PD-L1 and CD73 expression, impacting the anti-cancer immune response.

Clinical Trials (TICIMEL)

  • A phase 1b clinical trial (TICIMEL) with 32 melanoma patients combined nivolumab and ipilimumab with an anti-TNF agent (infliximab or certolizumab).
  • The addition of an anti-TNF agent to PD-1 and CTLA-4 immunotherapy shows clinical activity in melanoma patients.
  • The treatment regimen included an induction phase and a maintenance phase.

Safety Considerations

  • The combination therapies of ipilimumab, nivolumab, and anti-TNF agents have side effects.
  • Dose-limiting toxicities (DLTs) in the first 12 weeks were considered to assess safety, such as congestive cardiac failure, myocarditis, alterations in LVEF, Guillain-Barré Syndrome, and active mycobacterial infections.
  • Adverse events like vitiligo (depigmentation) were higher in the certolizumab cohort.

Impact and Mechanisms

  • TNF blockade in experimental mouse melanoma models improves anti-melanoma immune response and inhibits tumor growth.
  • This is associated with increased CD8 TIL (tumor infiltrating lymphocytes) content.
  • Anti-TNF enhances anti-PD-1 therapy, and preventing anti-PD-1 induced TIM-3 upregulation on TILS further improves outcomes.
  • TNF facilitates melanoma growth by impeding the CD8 T cell-dependent immune response.
  • TNF mediates activation-induced cell death of melanoma-infiltrating TILs upon anti-PD-1 therapy.

Summary

  • TNF has a complex role in melanoma, affecting both tumor growth and immune responses.
  • Anti-TNF therapies can enhance anti-tumor immune responses and clinical outcomes when combined with PD-1/CTLA-4.
  • Further research and study of TNF mechanisms are essential.
  • Safety profiles must be closely observed.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Quiz Team

Related Documents

Anti-TNF in Melanoma Immunotherapy: From Basic Findings to the Clinic PDF

Description

Explore the complex roles of TNF in melanoma immunotherapy, from its dual influence on tumor progression and immune response to its immunosuppressive functions. This quiz delves into basic findings, clinical implications, and the current state of clinical trials targeting TNF in melanoma treatment.

More Like This

Melanoma Awareness Quiz
5 questions

Melanoma Awareness Quiz

NobleStrait5938 avatar
NobleStrait5938
Melanoma Treatment Agents Overview
26 questions

Melanoma Treatment Agents Overview

InvaluableStatistics3928 avatar
InvaluableStatistics3928
Melanoma Uveal: Diagnóstico e Tratamento
82 questions

Melanoma Uveal: Diagnóstico e Tratamento

WellManneredMood avatar
WellManneredMood
Melanoma Treatment and Curcumin Benefits
52 questions

Melanoma Treatment and Curcumin Benefits

WillingBronze7024 avatar
WillingBronze7024
Use Quizgecko on...
Browser
Open
Browser
Browser