Module 5: Cancer and the Immune System

Anti-tumour antibodies enhance tumour growth

-act as a blocking factor to mask antigens from cytotoxic T cells (evade immune system) -They also inhibit antibody-dependent cell mediated Cytotoxicity by binding the antibody receptors on natural killer cells and macrophages = this overall blocks the body's ability to kill cancerous cells, thus enhancing tumour growth

Elimination

A variety of immune cells, including NK cells, cytotoxic T cells, and helper T cells can recognize the altered cell and work to eliminate it

Tumour cells provide poor costimulatory molecules

-T cells require both expression of MHC and costimulatory molecules to become activated -Tumour cells lack these constimulatory molecules, which may contribute to their poor immunogenicity -T cells will only be partially activated

Reduced MHC expression on Tumour Cells

-Tumour Cells display low levels of MHC class I molecules on their cell surface -Since cytotoxic T lymphocytes (CTLs) recognize antigens in the context of MHC class I molecules, an avsences of these molecules will inhibit recognition of tumour cells

Cancer-Immunity cycle

-describes how the immune system balances the recognition of, and defense against, nonself molecules and the prevention of autoimmunity -The goal of immunotherapy in cancer is to stimulate the Cancer-Immunity Cycle in individuals with cancer, without damaging healthy cells

Behave differently

-do not need specific growth factors to divide, that normal cells do -they also don't respond to the signals that cause normal cells to stop dividing - therefore they will continue to divide and grow, ultimately forming a tumour

Equilibrium

-if they are not eliminated they can enter a state of equilibirum where the cell proliferation is matched by cell killing by the immune system This equilibirum phase could alst for a short tiem or many years

Cancer immunoediting

-the ongoing cross-talk between cancer cells and the immune cells -the process that can either kill the tumour or promote tumour progression is consistuted by the three E's Elimination, Equilibrium, Escape

Release of cancer cell antigens (cancer cell death)

1. Antigens are relased by mutated cancer cells, indicating that they are not healthy cells -immune system is able to recognize these antigens

Tumour Immune Microenvironment

1. Inflammed (hot): respond better to chemotherapy and immunotherapy compared to the other type 2. Non-inflammed (cold) Based on T cell density and presence of increased levels of some interferon associated genes

Cancer antigen presentation (DC/APCs)

2. The cells of the immune system capture the released antigens and travel to the lymph nodes where they find teh T cells

Priming and activation (APCs & T cells)

3. T cells are activated by the antigens and the immune response against the cancer cells initiated

Trafficking of T cells into tumours (CTLs)

4. The activated T cells move through the blood vessels to the site of the tumour

Infiltration of T cells into tumours (CTLs , endothelial cells)

5. Once the T cells reach teh cancerous cells, they invade the tumour to attack it

Recognition of cancer cells by T cells (CTLs, cancer cells)

6. T cells recognize cancer cells becuase of teh antigens they had previously released

Killing of cancer cells (immune & cancer cells)

7. T cells initiate a pathway that results in cancer cell death

Escape

A cancer cell may escape elimination by thte immune system -Tumour cells are no longer recognized by the immune system so they can avoid elimination -these cells grow uncontrolled and eventually proliferate to form a tumour -an important feature of cancer is the ability to produce heterogeneous cells due to mutation

Cancer

Characterized by an error in either of the balances between cell grotwh and cell death -these changes result due to alterations in DNA which induce cell transformation - the change a normal cell undergoes as it becomes malignant -cancer cells are viewed as self cells that have been altered to escape the normal growth-regulating mechanisms

Malignant tumour

Is cancerous and has the ability to spread to, and invade surrouding tissue (metastasize). These tumours continue to grow and become rogressively invasive

Tumor Infiltrating Lymphocytes (TILs)

T cells are shown and are the most effective lymphocytes in killing cancer cells - B lymphocytes are also important = broadly termed TILs -the type, density, and location of TILs has been suggested as a prognostic biomarker in some cancers -These TILs leave the blood stream and migrate to infiltrate the tumour under influence of various chemotactic gradients, mostly, CXC chemokines -TILs can be a mix of T and B cells -NK cells, DCs, and Macrophages are sometimes relevant as well

Immunotherapy

New treatment method that works to boost an individual's immune system in response to cancer via targeting a variety of immune functions including: recognition of abnormal cells/potentially cancerous cells -initiation of the immune response -Strength of the immune response -could be effective cause it is able to attack cancerous cells throughout all the organs in the body -allows to specifically taget and eliminate cancer cells without damaging healthy cells, resulting in fewer side effects than traditional cancer treamtnes -takes advantage of immunological memory

Metastasis

The colonization by tumour cells of sites different from their primary site of origin -small clusters of cancerous cells will break off from the tumour and invade the surrounding blood or lymphatic vessels, travelling to different areas of the body, where they can proliferate

Benign tumour

Not cancerous, this type of tumour is unable to grow indefinietly or invade surrounding tissues

What functions of the immune system do you think would be important in treating cancer

The immune systems ability to detect and eliminate abnormal cells can lead to the prevention of many cancers -however, cells often develop the ability to avoid detection by the immune system Can be used to treat cancer tumour in steps 2 and 7 of the C-I C

The tumour immunosurveillance theory

the tumour cells are identified and kept under control by the immune system -However, cancer cells sometimes evade recognition by the immune system, or the magnitude of the anti-tumour immune response is not sufficient to kill all the caner cells

TILs and Immunoscore

measures the density/numbers of CD3+ and CD8+ T cells int he centore of the tumour (CT) and at their periphery of the tumour (IM) by immunohistochemistry