Immune Response to Tumors: Tumor Antigens and Antitumor Immunity

by Peter Delves, PhD

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    00:01 So let’s turn now away from tumors of the immune system itself, and ask the question - does the immune system naturally prevent or attack cancers? Well the answer is yes, but perhaps only for certain cancers.

    00:20 So what is the evidence that the immune system can actually recognize and attack cancers.

    00:26 Well there’s an increased incidence of certain cancers in patients with immunodeficiency, including immunosuppressed transplant patients as we’ve just mentioned.

    00:38 The term immunosurveillance is used.

    00:41 And this relates to the concept that cells of the immune system patrol around the body looking for cells that have become abnormal because of malignant transformation.

    00:53 Certainly the immune system can prevent tumors that are linked to oncogenic pathogens.

    00:59 And it’s now known that a number of organisms can trigger the development of tumors.

    01:06 So for example, the virus HTLV1 (Human T-cell Leukemia Virus-1) as the name suggests, is responsible for inducing T-cell leukemia.

    01:17 Epstein-Barr virus can trigger a number of tumors including Burkitt’s lymphoma, nasopharyngeal carcinoma and post-transplant lymphoma.

    01:28 The Human Papilloma viruses 16 and 18 are responsible for triggering cervical cancer and penile cancer.

    01:37 Hepatitis B virus and Hepatitis C virus are linked to the development of liver cancer.

    01:43 And the bacterium Helicobacter pylori can trigger the development of stomach cancer.

    01:49 So it’s quite clear in these kind of situations where infectious agents are linked to the development of a tumor.

    01:56 And after all the immune response has developed, has evolved to fight infectious agents.

    02:02 One can see a clear potential role for the immune system in this kind of situation.

    02:10 The term tumor antigen is used to describe antigens that are associated with tumor cells.

    02:18 Remember, tumors are derived from normal cells.

    02:25 Tumor-associated antigens are antigens that are present either in or on normal cells.

    02:34 And the immune system will normally be tolerant to such antigens, because they’re normal self antigens.

    02:42 In contrast, tumor-specific antigens are restricted to tumor cells, and the immune system may well not be tolerant to such antigens; perhaps arising by mutations in a gene that then encodes a different form of a protein to which the individual has not been made immunologically tolerant.

    03:07 There are a number of different types of tumor antigen.

    03:11 Some of the products have mutated oncogenes or tumor suppressor genes.

    03:16 Examples of ongogene products include RAS mutations that are seen in around about 10% of human carcinomas, the p210 product of the Bcr/Abl rearrangements that can occur in chronic myeloid leukemia.

    03:32 And mutations of tumor suppressor gene products, such a p53 mutations which are present in around about 50% of human tumors.

    03:42 There are also tumor antigens that are unmutated but overexpressed products of oncogenes.

    03:50 The HER2/Neu antigen is a good example of this that is seen in breast and other carcinomas.

    03:58 Mutated forms of cellular genes that are not themselves actually involved in tumorigenesis, can act as tumor antigens.

    04:05 For example, various mutated proteins that are found in melanomas that are recognized by cytotoxic T-lymphocytes.

    04:13 And then we also have the products of genes that are silent in most normal tissues.

    04:18 For example, the cancer/testis antigens expressed in melanomas and many carcinomas.

    04:24 These antigens are normally expressed mainly in the testis and placenta, but can get expressed in tumor cells.

    04:32 Tumor antigens can also be normal non-oncogenic proteins that are overexpressed in tumor cells.

    04:38 For example, tyrosinase, gp100, and the MART antigens that are found in melanomas and are normally expressed in melanocytes.

    04:50 They can be the products of oncogenic viruses.

    04:52 For example, the papilloma virus E6 and E7 proteins that are associated with cervical carcinomas.

    05:00 EBNA-1 protein of Epstein-Barr virus, present in EBV-associated lymphomas and in nasopharyngeal carcinoma.

    05:10 Oncofetal antigens, such as the carcinoembryonic antigen that’s present in many tumors, and also expressed in liver and other tissues during inflammation.

    05:22 And another example of an oncofetal antigen is alphafetoprotein.

    05:28 Glycolipids and glycoproteins can also act as tumor antigens.

    05:32 For example, the GM2 and GD2 antigens on melanomas.

    05:38 And then finally, differentiation antigens that are normally present in the tissue of origin.

    05:44 For example, the prostate specific antigen (PSA) present in prostate carcinomas.

    05:49 And another example here would be CD20 on B-cell lymphomas.

    05:55 Anti-tumor immunity is essentially the same kinds of responses that we see against infectious agents.

    06:02 So antibody together with complement, the antibody can bind to tumor antigens present on the surface of the tumor cell, activate complement.

    06:12 And the membrane attack complex can destroy the tumor cell.

    06:17 Antibody dependant cellular cytotoxicity (ADCC), again an antibody against a tumor antigen expressed on the surface of the tumor cell can be recognized by cells that are capable of mediating ADCC.

    06:33 We call such cells, killer cells; really they can be any cell in the immune system that has an Fc receptor and also is able to fuse toxic molecules.

    06:43 And most cells in fact in the immune system can carry out this function of ADCC.

    06:48 There can be direct natural killer cell cytotoxicity, where the killer activating receptors on the surface of natural killer cells recognize ligands on the surface of the tumor cell.

    07:03 And finally there can be cytotoxic T-cells which recognize tumor-derived peptides presented by MHC Class I molecules.

    07:13 It’s very clear that immune system cells are naturally present within tumors.

    07:18 We can find T-cells, natural killer cells, macrophages, also regulatory T-cells and myeloid derived suppressor cells within tumors.

    07:33 So T-cells, natural killer cells and macrophages potentially could mediate a beneficial anti-tumor response.

    07:41 One of the problems is that very often, these other cell types, such as regulatory T-cells and myeloid derived suppressor cells actually dampen down the anti-tumor response.

    About the Lecture

    The lecture Immune Response to Tumors: Tumor Antigens and Antitumor Immunity by Peter Delves, PhD is from the course Tumor Immunology. It contains the following chapters:

    • The Immune Response to Tumors
    • Tumor Antigens
    • Anti-Tumor Immunity

    Included Quiz Questions

    1. Natural killer cells
    2. Macrophages
    3. B lymphocytes
    4. T lymphocytes
    5. Plasma cells
    1. Lung cancer - human papillomavirus 16
    2. Gastric cancer - Helicobacter pylori
    3. Liver cancer - hepatitis B virus
    4. Burkitt's Lymphoma - Epstein–Barr virus
    5. T-cell leukemia - human T-cell lymphotropic virus type 1
    1. BCR/ABL rearrangement in chronic myeloid leukemia
    2. Tyrosinase in melanoma
    3. gp100 in melanoma
    4. HER2 in breast cancer
    5. Papillomavirus proteins in cervical cancer
    1. Myeloid-derived suppressor cells
    2. T cells
    3. Natural killer cells
    4. Macrophages
    5. Neutrophils

    Author of lecture Immune Response to Tumors: Tumor Antigens and Antitumor Immunity

     Peter Delves, PhD

    Peter Delves, PhD

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    By Kishore Krishna Kumaree .. on 08. October 2019 for Immune Response to Tumors: Tumor Antigens and Antitumor Immunity

    very nice and descriptive information regarding the tumor immunology, it has helped a lot