Podcast
Questions and Answers
What is the primary role of Tumor Necrosis Factor (TNF) in cancer?
What is the primary role of Tumor Necrosis Factor (TNF) in cancer?
TNF has been solely associated with increasing tumor progression without any benefits.
TNF has been solely associated with increasing tumor progression without any benefits.
False
Who is the professor associated with the research on ANTI-TNF in melanoma immunotherapy?
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.
The clinical trial TICIMEL focuses on advanced melanoma patients and is classified as a phase _____ trial.
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Match the following terms with their corresponding roles in melanoma treatment:
Match the following terms with their corresponding roles in melanoma treatment:
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What is one of the functions of TNF in the context of cancer?
What is one of the functions of TNF in the context of cancer?
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Chronic inflammation is associated with tumor progression and metastasis.
Chronic inflammation is associated with tumor progression and metastasis.
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What does MDSC stand for in the context of immunosuppression?
What does MDSC stand for in the context of immunosuppression?
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TNF has pleiotropic functions in anti-cancer immune response, including in __________.
TNF has pleiotropic functions in anti-cancer immune response, including in __________.
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Match the following cancer-related factors with their effects:
Match the following cancer-related factors with their effects:
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Which of the following is NOT a function of TNF related to cancer cells?
Which of the following is NOT a function of TNF related to cancer cells?
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Lymphocyte-mediated cytotoxicity is unrelated to TNF's function in anti-cancer immune response.
Lymphocyte-mediated cytotoxicity is unrelated to TNF's function in anti-cancer immune response.
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The process of __________ involves the migration of leukocytes into tumors.
The process of __________ involves the migration of leukocytes into tumors.
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What type of molecules are involved in Treg and Breg adhesion as referenced in the JCI 2012?
What type of molecules are involved in Treg and Breg adhesion as referenced in the JCI 2012?
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Ipilimumab is used as a monotherapy in melanoma immunotherapy.
Ipilimumab is used as a monotherapy in melanoma immunotherapy.
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What percentage of patients experienced complete response when treated with the combined immune checkpoint inhibitor?
What percentage of patients experienced complete response when treated with the combined immune checkpoint inhibitor?
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The anti-cancer immune response in melanoma includes the expression of ______ which interacts with immune checkpoints.
The anti-cancer immune response in melanoma includes the expression of ______ which interacts with immune checkpoints.
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Match the following terms with their appropriate descriptions:
Match the following terms with their appropriate descriptions:
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What type of adverse events are most commonly seen in patients receiving immune checkpoint inhibitors?
What type of adverse events are most commonly seen in patients receiving immune checkpoint inhibitors?
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Melanoma dedifferentiation involves the gain of melanocytic antigens.
Melanoma dedifferentiation involves the gain of melanocytic antigens.
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What is the role of anti-TNF therapy in patients with colitis caused by immunotherapy?
What is the role of anti-TNF therapy in patients with colitis caused by immunotherapy?
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What is the role of TNF blockade in mouse melanoma models?
What is the role of TNF blockade in mouse melanoma models?
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Anti-TNF therapy enhances anti-PD-1 therapy effectiveness against B16K1 melanoma.
Anti-TNF therapy enhances anti-PD-1 therapy effectiveness against B16K1 melanoma.
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What type of mice were used in the melanoma experiments?
What type of mice were used in the melanoma experiments?
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Etanercept is a drug that blocks _____ in melanoma treatment.
Etanercept is a drug that blocks _____ in melanoma treatment.
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Match the treatment with its effect:
Match the treatment with its effect:
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What was the primary effect measured in the studies involving Etanercept?
What was the primary effect measured in the studies involving Etanercept?
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The experiments utilized both WT mice and CD8 KO mice.
The experiments utilized both WT mice and CD8 KO mice.
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What does TILs stand for?
What does TILs stand for?
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The main immune cells measured in response to melanoma treatments were _____ T cells.
The main immune cells measured in response to melanoma treatments were _____ T cells.
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The experiments confirmed that TNF facilitates melanoma growth by enhancing CD8 T cells.
The experiments confirmed that TNF facilitates melanoma growth by enhancing CD8 T cells.
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What does the abbreviation 'WT' stand for in the context of the mice used?
What does the abbreviation 'WT' stand for in the context of the mice used?
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The immune response was assessed at _____ days in the study.
The immune response was assessed at _____ days in the study.
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Which of the following is NOT a focus of the studies involving TNF blockade?
Which of the following is NOT a focus of the studies involving TNF blockade?
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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.
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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.
