Immunotherapy Flashcards
(9 cards)
Redefinition of cancer through the lens of immunology?
Traditionally, cancer was viewed simply as a lesion that grows unchecked. This older view emphasized the abnormality of the cells themselves. However, modern immunology has reshaped this understanding. Today, cancer is increasingly defined not just by the presence of malignant cells, but by the failure of the host’s immune system to eliminate them. In this view, everyone harbors potentially malignant cells at some point, but these are usually kept under control by immune surveillance. Cancer, therefore, is not merely the cell, but the context — the failure of immune control mechanisms that allow such cells to proliferate.
Innate vs adaptive immune system?
Our immune defense is divided into two main systems. Innate immunity is the first line of defense, consisting of fast-acting, nonspecific cells like neutrophils, macrophages, and natural killer (NK) cells. These cells react quickly to abnormal changes but lack specificity. Adaptive immunity, on the other hand, involves highly specific responses from T-cells and B-cells, which take longer to activate but are tailored to particular threats. Dendritic cells are unique in that they serve as messengers between these two systems, sensing danger and helping to activate adaptive responses.
What is the tumor microenvironment?
When discussing tumors, it’s common to refer to the tumor immune microenvironment (TIME), but this term can be misleading. While the TIME is indeed rich in immune cells (T-cells, B-cells, NK cells, and myeloid cells), it also includes non-immune components like fibroblasts, endothelial cells, adipocytes, and mesenchymal stem cells. These non-immune cells can actively influence tumor progression or suppression, contributing to either an immune-activating or immune-suppressive environment.
Antigen presentation and T cell cooperation?
n tumor immunology, CD8+ T-cells are the main effectors that kill cancer cells. They recognize tumor antigens presented via HLA class I molecules. Meanwhile, CD4+ T-helper cells recognize antigens presented via HLA class II, primarily by dendritic cells. These helper cells are essential for supporting and activating CD8+ T-cells, which are often limited in number.
The role of B cells in cancer?
Though traditionally studied for their role in antibody production, B-cells are now being explored for their impact within tumors. Inside the tumor, B-cells may form structures similar to lymph nodes and begin producing antibodies locally. Normally, B-cells capture antigens via their B-cell receptor, process them, and present them via HLA II to CD4 T-helper cells. These helper cells then secrete cytokines (like IL-2, IL-4, IL-5), which stimulate further B-cell activation and antibody production.
Neutrophils in cancer?
Neutrophils, key players in innate immunity, come in two major phenotypes: N1 (anti-tumor) and N2 (pro-tumor). N1 neutrophils kill tumor cells by releasing reactive oxygen species (ROS).
On the other hand, N2 neutrophils support tumor growth by suppressing T-cells via Arginase-1, which depletes arginine — a critical nutrient for T-cell function — and by promoting angiogenesis via VEGF.
PD1 signaling and its immunosuppressive role?
PD-1 is a key immune checkpoint receptor expressed on T cells. It plays a suppressive role in the immune system by blocking both the primary and secondary activation signals in T cells. The first signal, involving TCR CD3-ZAP70, is essential for T cell activation, while the second signal, CD28-PI3K, promotes proliferation and survival. PD-1 inhibits both via recruitment of SHP-2, a phosphatase that blocks ZAP70 and CD28 pathways. This suppresses T cell responses in chronic inflammation and cancer.
Anti CTLA4 therapy?
CTLA-4 is another immune checkpoint that downregulates T cell responses, mainly in the priming phase (in lymph nodes) and also in the effector phase (within tumors). It is highly expressed on T regulatory cells. Anti-CTLA-4 antibodies like ipilimumab can block CTLA-4 on Tregs and also induce antibody-dependent cellular cytotoxicity via Fc receptors on macrophages, NK cells, and neutrophils—leading to Treg depletion in the tumor. This helps reduce immunosuppression and promotes a more active anti-tumor immune environment. Though debated, many believe this mechanism occurs in humans, particularly in patients who respond to therapy.
Examples of Mabs and their use?
Cetuximab : anti ECGR approved for colon cancer, SCC of head and neck.
Bevacizumab : Targets angiogenesis through VEGF, approved for colorectal cancer, renal cancer, ovarian cancer, NSCLC and GBM.
Transtuzumab : Anti HER2, used in HER2+ breast and gastric cancer.
Durvalumab : anti PD1 used in bladder cancer and unresectable NSCLC.
Ipilimumab : Anti CTLA4, approved for metastatic melanoma and renal cancer.
Atezolizumab : anti PD1 used in bladder, breast and NSCLC
Nivolumab : Anti PD1 approved for melanoma. RCC and HCC.
Rituximab : anti CD20
