Podcast
Questions and Answers
A tumor cell population demonstrates reduced MHC class I expression combined with MIC expression. How would you expect NK cells to respond to this population compared to a population with low/normal MHC class I and no MIC expression?
A tumor cell population demonstrates reduced MHC class I expression combined with MIC expression. How would you expect NK cells to respond to this population compared to a population with low/normal MHC class I and no MIC expression?
- The low MHC class I/MIC expressing population will be more susceptible to NK cell-mediated killing. (correct)
- Both populations will be equally susceptible to NK cell-mediated killing, as MHC class I downregulation is the dominant factor.
- The low/normal MHC class I/no MIC expressing population will be more susceptible because they are able to shed MIC.
- Neither population will be susceptible, as NK cells require both the absence of MHC class I and the presence of MIC for activation.
A researcher observes that tumor cells are not effectively eliminated by cytotoxic T lymphocytes (CTLs). Which mechanism would LEAST likely explain this phenomenon?
A researcher observes that tumor cells are not effectively eliminated by cytotoxic T lymphocytes (CTLs). Which mechanism would LEAST likely explain this phenomenon?
- The tumor cells actively secrete cytokines that inhibit CTL activity.
- The tumor cells lack sufficient tumor-associated antigens for CTL recognition.
- The tumor cells have upregulated the expression of ligands that activate NK cells. (correct)
- The tumor cells express low levels of MHC class I molecules.
Which mechanism primarily explains how tumor-induced upregulation of PD-L1 on tumor cells leads to immune evasion?
Which mechanism primarily explains how tumor-induced upregulation of PD-L1 on tumor cells leads to immune evasion?
- Promoting the differentiation of tumor-associated macrophages (TAMs).
- Recruiting myeloid-derived suppressor cells (MDSCs) to the tumor microenvironment.
- Enhancing antigen presentation to T cells.
- Inhibiting T cell activation and effector function. (correct)
A patient's tumor biopsy reveals a high infiltration of regulatory T cells (Tregs) within the tumor microenvironment. Which cytokine is MOST likely responsible to have caused this observation?
A patient's tumor biopsy reveals a high infiltration of regulatory T cells (Tregs) within the tumor microenvironment. Which cytokine is MOST likely responsible to have caused this observation?
Tumor cells can evade recognition and killing by NK cells through various mechanisms. Which strategy would be LEAST effective for tumor cells to avoid NK cell-mediated cytotoxicity?
Tumor cells can evade recognition and killing by NK cells through various mechanisms. Which strategy would be LEAST effective for tumor cells to avoid NK cell-mediated cytotoxicity?
A research study investigates a novel cancer therapy targeting the tumor microenvironment. The therapy aims to block the recruitment and activity of myeloid-derived suppressor cells (MDSCs). Which outcome would BEST indicate the therapy's success?
A research study investigates a novel cancer therapy targeting the tumor microenvironment. The therapy aims to block the recruitment and activity of myeloid-derived suppressor cells (MDSCs). Which outcome would BEST indicate the therapy's success?
Following treatment with IFN-γ, a patient's tumor cells exhibit increased expression of MHC class I molecules. How would this change affect recognition and killing of tumor cells by CD8+ T cells and NK cells?
Following treatment with IFN-γ, a patient's tumor cells exhibit increased expression of MHC class I molecules. How would this change affect recognition and killing of tumor cells by CD8+ T cells and NK cells?
A researcher is investigating why certain tumor cells are resistant to T cell-mediated killing, despite expressing tumor-associated antigens. Which mechanism would BEST explain tumor resistance, assuming normal antigen processing and presentation?
A researcher is investigating why certain tumor cells are resistant to T cell-mediated killing, despite expressing tumor-associated antigens. Which mechanism would BEST explain tumor resistance, assuming normal antigen processing and presentation?
A patient's cancer cells are found to undergo antigenic variation, resulting in the presentation of different peptide-MHC complexes over time. How will this variation affect the ability of the patient's T cells to recognize and kill tumor cells?
A patient's cancer cells are found to undergo antigenic variation, resulting in the presentation of different peptide-MHC complexes over time. How will this variation affect the ability of the patient's T cells to recognize and kill tumor cells?
A new cancer immunotherapy aims to enhance the adaptive immune response against tumors by promoting the expression of MHC class I molecules. Besides administering IFN-γ, the researchers considered other approaches. Which of the following potential strategies would antagonize the intended effect of that immunotherapy?
A new cancer immunotherapy aims to enhance the adaptive immune response against tumors by promoting the expression of MHC class I molecules. Besides administering IFN-γ, the researchers considered other approaches. Which of the following potential strategies would antagonize the intended effect of that immunotherapy?
Flashcards
MHC Class I Reduction
MHC Class I Reduction
Tumor cells evade CTLs by reducing MHC class I molecules, thus avoiding T cell recognition and destruction.
Low Immunogenicity
Low Immunogenicity
Tumors avoid immune detection by not producing enough tumor-specific antigens (TSAs) or tumor-associated antigens (TAAs) that the immune system can recognize.
Antigenic Modulation
Antigenic Modulation
Tumor cells lose or alter tumor antigens recognized by immune cells, enabling escape from immune recognition.
Tumor-Induced Immune Suppression
Tumor-Induced Immune Suppression
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NK Cell Response to MHC-I Downregulation
NK Cell Response to MHC-I Downregulation
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CD8+ T Cell Surveillance Role
CD8+ T Cell Surveillance Role
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IFN-γ and MHC-I Upregulation
IFN-γ and MHC-I Upregulation
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Escape from CTL Recognition
Escape from CTL Recognition
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Tumor Immune Evasion: Shedding MIC
Tumor Immune Evasion: Shedding MIC
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Study Notes
MHC Class I and CTL Responses
- Immune complexes can block cytotoxic T lymphocyte (CTL) responses.
- Alterations in MHC class I molecule expression on tumor cells affect CTL-mediated killing, which is critical for anti-tumor cell regulation.
- Reduction of MHC class I molecules on tumor cells can control CTLs.
- Malignant transformation is linked to decreased or complete loss of MHC class I molecules.
Tumor Microenvironment and MHC Class I Expression
- The immune response within the tumor microenvironment can select tumor cells with reduced MHC class I expression.
- Tumor cells with high MHC class I levels are eliminated by CTLs.
- Tumor cells expressing moderate to low MHC molecule levels may evade CTL-mediated destruction.
MHC Class I and Immune Evasion
- CTL recognition and destruction of tumor cells requires the presence of MHC class I molecules.
- Cancerous agents can evade the immune system by reducing MHC class I expression, avoiding CTL attacks.
- Some tumor cells reduce surface protein expression to evade recognition by host immune cells.
T Cell Activation and Tumor Immunogenicity
- T cell activation needs an activating signal, including a post-stimulatory signal, in addition to interaction with the antigen MHC complex.
- Poor tumor cell immunogenicity results in a lack of post-stimulatory molecules, limited post-indirect activity, and failure to activate T cells, leading to anergy.
MHC Class I, MIC, and NK Cell Activity
- Analysis of tumor cells revealed some had lower MHC I expression, but expressed MIC, while others had normal levels of MHC I and no MIC.
- High levels of MHC class I molecules reduce NK cell-induced death of target tumor cells.
- Killer-cell Immunoglobulin-like Receptor (KIR) inhibitory receptors on NK cells bind to MHC class I, inhibiting target cell death via signal transduction.
- Reduced MHC class I paired with MIC protein presence increases NK cell-mediated tumor cell death.
- MIC proteins bind to activating receptors on NK cells, inducing cell death of targeted tumor cells.
Mechanisms of Tumor Immune Evasion
- Tumors use low immunogenicity, antigenic modulation, and tumor-induced immune suppression to evade immune recognition.
Low Immunogenicity
- Tumors avoid immune detection by not producing enough tumor-specific antigens (TSAs) or tumor-associated antigens (TAAs).
- Low MHC molecule expression prevents proper antigen presentation to T cells, hindering tumor recognition.
- Downregulation of stress-induced ligands like MIC prevents activation of the innate immune system and NK cells.
- Tumors express low levels of MHC class I to reduce antigen presentation.
- Tumor cells downregulate ligands recognized by NK cells, escaping NK cell targeting.
Antigenic Modulation
- Tumor cells undergo antigenic modulation via loss or alteration of tumor antigens recognized by immune cells.
- Antigenic variation and mutations alter epitopes presented by MHC molecules, preventing T cell recognition.
Tumor-Induced Immune Suppression
- Tumors create an immunosuppressive microenvironment that inhibits immune cell activity.
- Tumor cells release TGF-β and other cytokines that induce the differentiation of regulatory T cells (Tregs).
- Tregs suppress effector T cell activity, preventing them from attacking the tumor.
- Tumors recruit myeloid-derived suppressor cells (MDSCs), immunosuppressive cells that inhibit T cells, NK cells, and other immune cells.
- Tumor-associated macrophages (TAMs) promote tumor growth, angiogenesis, and suppress anti-tumor immune responses via cytokines like IL-10 and TGF-β.
NK Cell Susceptibility
- Tumor cells with low MHC class I expression and MIC expression are susceptible to NK cells.
- Tumor cells with low/normal MHC and no MIC expression are not susceptible to NK cells.
- Absence of MIC on some may indicate MIC shedding, which is also a method of tumor evasion of immune responses.
- Shed MIC activates NK cells, but because they are not in contact with target cells, they do not kill.
MHC Class I Downregulation
- NK cells recognize and kill cells lacking or with reduced MHC-I expression via receptors.
- Reduced MHC-I levels activate NK cells, causing target cell killing.
Adaptive Immune Response
- CD8+ T cells can recognize and respond to viral or tumor antigens presented on MHC-I.
- The adaptive immune response continually scans for cells with abnormal MHC-I expression (immunosurveillance.)
Interferon-Gamma Induction
- IFN-γ upregulates MHC-I expression and is a key cytokine.
- During infections, CD8+ T cells produce IFN-γ - promoting MHC-I expression (positive feedback).
Immunotherapies
- Checkpoint inhibitors targeting PD-1/PD-L1 or CTLA-4 enhance the immune response against cancer cells.
- Therapies block inhibitory signals, restoring T cell activity against cancer, even with altered MHC-I expression.
Consequences of MHC-I Downregulation
- Reduced MHC-I expression hinders CTL recognition and elimination of infected or cancerous cells.
- NK cells recognize and eliminate cells with altered MHC-I expression.
- MHC-I downregulation challenges immune surveillance, allowing viruses and cancer cells to evade detection.
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