Tumor Immunology


immune system and tumor cells

Tumor immunology describes the interaction between cells of the immune system with tumor cells. Understanding the role of the immune system in the progression and development of cancer is important for the development of new therapies for cancer treatment.

Tumor Antigens:

The question of whether human tumors express antigens that can be recognized by the immune system has been answered with a resounding YES.

Many tumor cells produce antigens, which may be released in the bloodstream or remain on the cell surface. Antigens have been identified in most of the human cancers, including Burkitt lymphoma, neuroblastoma, melanoma, osteosarcoma, renal cell carcinoma, breast cancer, prostate cancer, lung carcinoma, and colon cancer. A key role of the immune system is the detection of these antigens to permit subsequent targeting for eradication.

However, despite their foreign structure, the immune response to tumor antigens varies and is often insufficient to prevent tumor growth.

Tumor-associated antigens (TAAs) are relatively restricted to tumor cells.

Tumor-specific antigens (TSAs) are unique to tumor cells.

TSAs and TAAs typically are portions of intracellular molecules expressed on the cell surface as part of the major histocompatibility complex.

Tumor Immunology

Suggested mechanisms of origin for tumor antigens include:

  • Introduction of new genetic information from a virus (eg, human papillomavirus E6 and E7 proteins in cervical cancer).
  • Alteration of oncogenes or tumor suppressor genes by carcinogens, which result in the formation of neoantigens (novel protein sequences or accumulation of proteins that are normally not expressed or are expressed at very low levels, such as ras or p53), either by generating the novel protein sequence directly or by inducing accumulation of these proteins.
  • Missense mutations in various genes not directly associated with tumor suppressor or oncogenes and that cause the appearance of tumor-specific neoantigens on the cell surface.
  • Abnormally high levels of proteins that normally are present at substantially lower levels (eg, prostate-specific antigens, melanoma-associated antigens) or that are expressed only during embryonic development (carcinoembryonic antigens).
  • Uncovering of antigens normally buried in the cell membrane because of defective membrane homeostasis in tumor cells.
  • Release of antigens normally sequestered within the cell or its organelles when tumor cells die.

Some recent evidence links immune response in cancer patients to mutations in tumor cells.

References:

Dmitry Gabrilovich, Christopher M. Davis. Tumor Antigens – Hematology and Oncology – Merck Manuals Professional Edition https://www.merckmanuals.com/en-ca/professional/hematology-and-oncology/tumor-immunology/tumor-antigens

Snyder A, Makarov V, Merghoub T, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. New Engl J Med 37:2189–2199, 2014. doi: 10.1056/NEJMoa1406498.

Van Allen EM, Miao D, Schilling B, et al. Genomic correlates of response to CTLA-4 blocker in metastatic melanoma. Science 350:207–211, 2015. doi: 10.1126/science.aad0095.

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