Oncology MCQ 2

A protein complex consisting of Cyclin B and Cdk1, which is crucial for regulating the transition from the G2 phase to the M phase of the cell cycle, promoting cell division.

Unique protein fragments found on tumor cells that are not present in normal cells. These neoantigens are recognized by the immune system as foreign, making them potential targets for immunotherapy.

A form of immunotherapy that involves genetically modifying a patient's immune cells (T cells) to express a chimeric antigen receptor (CAR) that specifically targets cancer cells.

The practice of introducing a weakened or inactive form of a pathogen into the body to stimulate an immune response and provide protection against disease.

William Coley observed that a patient with osteosarcoma experienced spontaneous tumor remission after contracting erysipelas, a bacterial infection. This led him to hypothesize that infections could boost the immune system's ability to fight cancer.

A theory proposing that the immune system actively monitors and eliminates cancerous cells, acting as a surveillance mechanism to prevent tumor development.

Paul Ehrlich, a German immunologist, first proposed the immunosurveillance theory in the early 20th century.

A phase in the immunoediting theory where a balance is established between the immune system and the tumor. The immune system exerts selective pressure, preventing uncontrolled tumor growth but not completely eradicating the cancer cells.

The elimination phase of immunoediting involves the immune system actively targeting and destroying tumor cells, primarily through the action of cytotoxic T cells and natural killer cells.

Neoantigens are unique to tumor cells and help the immune system recognize cancer. They are not derived from normal cell proteins.

Allergies are immune reactions triggered by the misrecognition of harmless compounds, such as pollen or dust, as harmful invaders.

The escape phase of immunoediting marks the point where tumor cells evolve mechanisms to evade the immune system's control, leading to uncontrolled tumor growth.

Dendritic cells are specialized antigen-presenting cells that engulf foreign substances and present them to T cells, initiating adaptive immune responses.

The immunosurveillance theory is limited by its difficulty explaining tumor progression in immunocompetent individuals, suggesting that the immune system alone may not be sufficient to prevent all cancer development.

The neoantigen-MHC complex is a crucial molecule on tumor cells that allows T cell recognition via the T cell receptor (TCR). This complex presents neoantigens to the TCR, triggering immune responses.

IFN-γ is a cytokine that plays a critical role in tumor immunity by inducing tumor cell apoptosis and attracting other immune cells to the site of the tumor.

The equilibrium phase of immunoediting is often clinically silent because the immune system maintains a delicate balance with the tumor, preventing significant tumor growth and avoiding overt symptoms.

Adaptive immunity is characterized by its specificity for antigens and the ability to remember past encounters with pathogens, leading to a faster and more effective response upon re-exposure.

During the equilibrium phase, tumor cells evolve new mechanisms to evade immune detection, such as downregulating MHC-I molecules or expressing immunosuppressive molecules, due to the selective pressure exerted by the immune system.

Heat shock proteins and IFN-γ are danger signals released by stressed or damaged cells, attracting immune cells to the site of early tumor growth.

Coley's toxin demonstrates that infections can boost immune responses against tumors, suggesting a potential therapeutic approach for cancer.

The thymus is a primary lymphoid organ where T cells undergo maturation and selection. It eliminates self-reactive T cells, preventing autoimmune reactions.

Innate immunity is characterized by its immediate and non-specific response to pathogens. It acts as the first line of defense, relying on pre-existing mechanisms to recognize and fight off infections.

Tumors can evade recognition by T cells by downregulating MHC-I molecules, the primary pathway for presenting antigens to T cells. This reduces the ability of T cells to recognize the tumor as foreign.

Cancer-associated fibroblasts (CAFs) secrete a variety of factors, including collagen, which forms a protective barrier around the tumor, making it difficult for immune cells to infiltrate and attack cancer cells.

VEGF is a key player in tumor immune escape by promoting angiogenesis, the formation of new blood vessels. This allows the tumor to grow and spread, while also reducing the adherence factors that attract immune cells.

Tumors resist apoptosis mediated by T cells by downregulating Fas (a death receptor) and upregulating FasL (a death ligand). This allows tumor cells to evade the cytotoxic effects of Fas-mediated apoptosis, enabling them to survive.

The Warburg effect describes a phenomenon where tumors preferentially rely on glycolysis for energy production even in the presence of oxygen. This metabolic shift allows tumors to grow rapidly and escape immune surveillance.

Immune cells become anergic in the tumor microenvironment due to the lack of oxygen and glucose, which creates a metabolically challenging environment for immune cells, suppressing their activity.

Lactate production by tumors lowers the pH of the tumor microenvironment. This acidic environment inhibits immune cell function, making it difficult for immune cells to effectively attack cancer cells.

Hypoxia, or low oxygen levels, in the tumor microenvironment suppresses immune cell activity. Immune cells are sensitive to oxygen levels, and a lack of oxygen can impair their function.

IL-10 is a cytokine involved in suppressing T-cell activity and increasing their sensitivity to apoptosis. It contributes to tumor immune evasion by promoting an immunosuppressive environment.

Macrophages, under tumor-induced conditions, undergo a transformation from M1 macrophages (anti-tumor) to M2 macrophages (pro-tumor). This M2 polarization contributes to tumor immune suppression.

Tumors interfere with immune cell navigation by producing non-functional ligands that block CXCR3, a chemokine receptor essential for immune cell migration towards the tumor.

Regulatory T cells (Tregs) suppress immune responses, promoting tumor immune suppression. They dampen the activity of other immune cells, allowing the tumor to evade immune surveillance.

Fibroblast conversion into CAFs builds a protective barrier around the tumor, forming a dense network of collagen that impedes immune cell infiltration. This physical barrier makes it difficult for immune cells to reach and attack cancer cells.

When CD4 T-cells are converted in the tumor microenvironment, they often transform into regulatory T cells (Tregs). This shift contributes to the immunosuppressive environment that allows tumors to escape immune control.

Tumors can suppress NK cell activity by upregulating soluble ligands. These ligands bind to NK cell receptors, inhibiting their cytotoxic function and preventing NK cells from effectively attacking cancer cells.

Tumors promote the metabolic inhibitory mechanism by increasing lactate production and reducing oxygen availability. This creates a hostile environment for immune cells, making it difficult for them to function effectively.

T cells are particularly sensitive to glucose depletion in the tumor microenvironment. The lack of glucose impairs their function and ability to proliferate, making them less effective in fighting cancer.

The immune system can both promote and suppress tumor growth, acting as a double-edged sword in cancer development.

Tumor cells can induce apoptosis in immune cells at a distance by releasing exosomes containing FasL, a death ligand that binds to Fas receptors on immune cells, triggering programmed cell death.

Hypoxia, or low oxygen levels, in the tumor microenvironment suppresses immune cells, promotes angiogenesis (formation of new blood vessels), and contributes to a pro-tumor environment.

Immunotherapy aims to stimulate the immune system to recognize and attack cancer cells, leveraging the body's own defenses to fight the disease.

Cellular immunotherapy involves genetically modifying a patient's T-cells to express chimeric antigen receptors (CARs) that specifically target cancer cells.

CAR-T cells overcome MHC-I downregulation by recognizing entire proteins on tumor cell surfaces, bypassing the need for MHC-I presentation.

First-generation CAR-T cells lacked co-stimulatory signaling domains, leading to limited activation and persistence.

Second-generation CAR-T cells were improved by incorporating the CD28 co-stimulatory domain, which enhanced T-cell activation and persistence.

CD3 phosphorylation and ZAP70 recruitment are crucial for initiating T-cell activation, triggering a cascade of downstream signaling events.

The LAT-SLP76 signalosome amplifies T-cell signaling, ensuring strong and sustained activation, leading to effective anti-tumor response.

Second-generation CAR-T cells faced challenges with poor persistence and sensitivity to low antigen levels, making them less effective in some cases.

The IL-2 receptor domain was introduced in fifth-generation CAR-T cells to enhance cytokine production, boosting anti-tumor response and improving effectiveness.

Proof of concept in first-generation CAR-T cell development demonstrated the potential to activate T cells but also highlighted limitations, paving the way for further improvements.

Low antigen levels on tumor cells can limit CAR-T cell sensitivity, as these cells require high antigen thresholds for activation.

Tumor antigen variance with reduced surface expression is a major cause of relapse in CAR-T therapy, as CAR-T cells may no longer recognize the modified tumor cells.

Second-generation CAR-T cells combine the CD3ζ signaling domain for activation with the CD28 co-stimulatory domain for enhanced signaling.

CAR receptors differ from TCRs by recognizing entire proteins on the tumor surface, rather than relying on MHC-I presentation for recognition.

ZAP70 plays a crucial role in amplifying T-cell signaling by phosphorylating LAT, a key molecule that triggers a cascade of downstream events.

First-generation CAR-T cells failed in clinical trials due to excessive toxicity and failure to form memory T-cells, leading to short-lived effectiveness and potential harm.

Second-generation CAR-T cells became more effective by integrating co-stimulatory signals (Signal 2), enhancing T-cell activation and persistence, leading to improved anti-tumor response.

LAT phosphorylation in CAR-T cells indicates complete signaling activation, confirming the successful engagement of the CAR receptor and initiation of the anti-tumor response.

Tumor relapse after initial success with CAR-T therapy often occurs because tumors evolve mechanisms to downregulate the antigen recognized by CAR-T cells, escaping immune detection.

Creating next-generation CAR-T cells faces the challenge of balancing sensitivity (recognizing tumor cells) with safety (avoiding off-target effects), ensuring effective treatment while minimizing harm.

Extracellular vesicles (EVs) are lipid bilayer-enclosed particles secreted by cells, acting as messengers that carry a cargo of molecules to other cells.

The primary function of EVs in cancer is to facilitate communication between tumor cells and the microenvironment, influencing tumor growth, spread, and immune evasion.

Tumor-derived EVs play a key role in cancer progression by delivering oncogenic molecules to recipient cells, promoting tumor growth and metastasis.

EVs can serve as biomarkers for cancer, reflecting the genetic and proteomic content of the tumor, providing valuable information for diagnosis and monitoring.

Density gradient centrifugation is commonly used to isolate EVs based on their size and density, allowing for purification and analysis.

Tumor-derived EVs can suppress immune responses by carrying inhibitory molecules, leading to immune evasion and promoting tumor growth.

Exosomes, a subtype of EVs, are typically 30-150 nm in size, smaller than microvesicles, and are involved in various cellular functions, including communication and signal transduction.

CD63 is a protein marker typically enriched in exosomes, often used to identify and track these small vesicles.

EVs contribute to the 'seed and soil' hypothesis of metastasis by modifying the microenvironment of distant organs, preparing a hospitable 'soil' for tumor cells to metastasize and grow.

Microvesicles are larger than exosomes, bud directly from the plasma membrane, and contribute to various cellular processes, including cell signaling and communication.

EV-mediated transfer of PD-L1 promotes immune evasion by suppressing T-cell function, allowing tumor cells to escape immune surveillance and grow.

Exosomal miRNAs can regulate gene expression in recipient cells, influencing tumor growth, angiogenesis, and drug resistance, contributing to cancer progression.

EVs contribute to therapy resistance in cancer by carrying drug efflux pumps, oncogenes, and anti-apoptotic molecules, enabling tumors to evade treatment.

Fluorescent labeling is a common method to track EV uptake in recipient cells, visualizing their distribution and interaction with target cells.

Tumor-derived EVs can convert M1 macrophages (anti-tumor) to M2 macrophages (pro-tumor), contributing to an immunosuppressive microenvironment that favors tumor growth.

EVs hold significant clinical potential in cancer as drug delivery vehicles, biomarkers for early diagnosis and monitoring, and therapeutic targets for inhibiting tumor progression.

EV heterogeneity, the diversity of EVs from different sources with overlapping properties, makes it challenging to isolate and characterize EVs for research and therapeutic applications.