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Questions and Answers
Which step in the Cancer Immunity Cycle involves the release of cancer cell antigens?
What could be a reason for a tumor to be classified as a 'Cold tumour'?
Why may T cells not properly home to tumors according to the text?
What is a characteristic of 'Immune-excluded tumours' based on the information provided?
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Which step in the Cancer Immunity Cycle involves the trafficking of T cells to tumors?
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What could be a factor contributing to the immuno-suppression of effector cells in the tumor microenvironment?
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What is a common characteristic of 'Cold tumours' based on the context provided?
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What could contribute to a tumor being categorized as 'Immune-excluded'?
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Why might DCs and T cells treat antigens as 'self' in cancer patients?
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What is the principal source of the extracellular matrix?
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Which cells are associated with enhanced proliferative, migratory, and secretory properties in the tumor microenvironment?
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Which type of lung cancer is the most common?
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What do M2 Macrophages support within tumors?
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Which factor is associated with T cell exclusion and poor response to anti-PD-L1 treatment?
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Which cells have been reported to enhance the recruitment of B cells through CXCL13 secretion?
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What is the role of FAP+ CAF depletion in tumors?
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'Loss-Of-Function CRISPR-Cas9 screening approach' aims to assess the impact of candidate genes on:
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What do M1 Macrophages support within tumors?
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What is the role of fibroblasts in forming a physical barrier around tumors?
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What is the purpose of adding fibroblasts to the tumor islets in the study?
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What does the 3D spheroid system aim to mimic?
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What is the main advantage of using 3D techniques over traditional 2D cell cultures?
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Which CAF subtype expresses a high level of α-smooth muscle actin (αSMA) and resides closely to the tumor?
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During which stage of lung adenocarcinoma do researchers observe a high presence of T cells and low presence of CAFs?
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What is the role of antigen-presenting CAFs (apCAFs) based on the text?
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How do researchers aim to exploit the plasticity of CAFs for therapeutic purposes?
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What is one key feature of the necrotic zone mentioned in the text?
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What is a distinctive characteristic of inflammatory CAFs (iCAFs) compared to other subtypes mentioned in the text?
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What is one factor that differentiates 3D techniques from traditional 2D cell cultures according to the provided text?
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What is one advantage of using 3D techniques over traditional 2D cell cultures in mimicking the tumor microenvironment?
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What is the primary purpose of adding fibroblasts to the tumor islets in the study described?
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How does the 3D spheroid system allow testing the effect of CAF-specific genes on T cell infiltration and tumor lysis effectively?
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What role do antigen-presenting CAFs (apCAFs) play based on the provided text?
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What could be a potential consequence of inhibiting antigen-presenting CAFs (apCAFs) within the tumor microenvironment?
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Which aspect of CAF plasticity is being explored for therapeutic purposes according to the text?
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What characteristic defines myofibroblastic CAFs (myCAFs) based on their location?
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What makes single-cell analysis studies essential in understanding CAF subtypes?
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What could be a potential downside of inhibiting myofibroblastic CAFs (myCAFs) in tumors?
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What is the principal function of fibroblasts in the tumor microenvironment?
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How can lung adenocarcinoma patients expressing high levels of TGFβ be more susceptible to treatment?
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Which type of lung cancer is more aggressive and prone to metastasis compared to non-small cell lung cancer?
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What would be a potential consequence of inhibiting all roles of cancer-associated fibroblasts (CAFs) in the tumor microenvironment?
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Why do small cell lung cancers have a higher metastatic potential compared to other lung cancer types?
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What is the main role of M2 Macrophages within tumors according to the text?
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How do circulating cancer-associated fibroblasts (CAFs) differ from typical fibroblasts?
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What is the primary function of CXCL13 secreted by cancer-associated fibroblasts (CAFs)?
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Why might fibroblasts around tumors pose a challenge for T cell and tumor cell interactions?
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What role do Cancer-associated fibroblasts (CAFs) play in immune checkpoint blockade therapy responsiveness?
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What might be a reason for the Cancer Immunity Cycle not performing optimally in cancer patients?
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What is a characteristic of 'Cold tumors' based on the Cancer Immunity Cycle information?
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What scenario would lead to a tumor being categorized as 'Immune-excluded'?
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What role do the factors in the tumor microenvironment play in suppressing effector cells?
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Which is a pattern associated with major T-cell infiltration in solid tumors?
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Why might cancer patients face challenges with tumor antigens being detected by DCs and T cells?
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What plays a key role in the Recognition of Cancer Cells by T cells during the Cancer Immunity Cycle?
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Study Notes
Cancer Immunity Cycle
- Generation of immunity is a cyclic process involving:
- Release of cancer cell antigens
- Cancer cell presentation (DCs/APCs)
- Priming and Activation (APCs + T cells)
- Trafficking of T cells to tumors (CTLs)
- Infiltration of T cells into tumors
- Recognition of cancer cells by T cells
- Ending with the killing of cancer cells, which increases cancer cell antigens and amplifies the process
Defects in Cancer Immunity Cycle
- In cancer patients, the cycle does not perform optimally due to:
- Tumor antigens may not be detected
- DCs and T cells may treat antigens as self-creating T regulatory cell responses
- T cells may not properly home to tumors and may be inhibited from infiltrating the tumor
- Factors in the tumor microenvironment might suppress the effector cells produced
T-cell Infiltration Patterns in Solid Tumors
- Major T-cell infiltration patterns observed:
- Cold tumor: lacks tumor antigen, inadequate priming, defects in antigen presentation, and/or lack of T-cell attracting chemokines
- Immune-excluded tumors: have immune evasion due to stromal barriers, lack of chemokines, aberrant vasculature, or hypoxia
Cancer-Associated Fibroblasts (CAFs)
- Abundant stromal cells in the tumor microenvironment
- Functional distinction from fibroblasts:
- Enhanced proliferative, migratory, and secretory properties
- More metabolically active, producing increased ECM factors
- Abnormal collagen production, often a more rigid and contractile pattern of collagen deposition
- Found in circulation, akin to circulating tumor cells (CTCs)
Role of CAFs in Regulating Tumor Immunity
- CAFs have multiple roles:
- Restricting the recruitment of immune effector cells such as CD8+ T cells into tumor tissues
- Central role in monocyte recruitment and the increased M2/M1 macrophage ratio
- CXCL13 secretion enhances the recruitment of B cells
- CAFs have both good and bad effects on cancer
CAFs and Tumor Immunity
- FAP+ CAF depletion/decrease induces T cell-mediated tumor regression
- CAF abundance is associated with poor prognosis
- TGFβ signature in CAFs: determinant of T cell exclusion and poor response to anti-PD-L1 (clinical trial)
Stromal Fibers and T Cell Infiltration
- Reduction in stromal fibers increases T cell infiltration and their contacts with tumor cell targets
- In some studies, depletion of CAFs results in immunosuppression and tumor progression
Lung Adenocarcinoma
- Leading cause of death from cancer in Canada
- 31,000 Canadians will be diagnosed with lung and bronchus cancer (13% of all new cancer cases in 2023)
- 20,600 Canadians will die from lung and bronchus cancer (24% of all cancer deaths in 2023)
- On average, 85 Canadians will be diagnosed with lung and bronchus cancer every day
Hypothesis and Aim
- Hypothesis: Cancer-associated fibroblasts (CAFs) play a key role in regulating T cell distribution at the tumor site
- Aim: Identify key CAF molecules that control/restrict T cell infiltration and target these factors to facilitate T cell infiltration and enhance anti-tumor adaptive immunity
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Description
Learn about the cancer immunity cycle process, including the release of cancer cell antigens, activation of T cells, trafficking of T cells to tumors, and killing of cancer cells. Understand how this cycle works and its implications for cancer patients.