Tumor antigens recognized by T lymphocytes

The purpose of T cell-mediated cancer immunotherapy is to reactivate these responses to a degree that results in tumor destruction without causing harmful effects on normal cells.

In other instances, the normal peptide is presented at the cell surface and consequently the T lymphocytes that recognize the antigen have been eliminated by the central tolerance process that occurs in the thymus.

An interesting example is gene fusions resulting from specific chromosomal translocations frequently encountered in certain types of cancer.

The gene fusion produces a chimeric protein segment from which a new antigenic peptide can be derived.

If the mutated cell divides significantly, the resulting clonal population may be eliminated by a T lymphocyte response.

[6] The contribution of these antigens to tumor immunogenicity is expected to vary according to the mutation rate: higher in lung carcinomas arising in tobacco smokers, in melanomas owing to mutations induced by UV and in the 15% of colorectal carcinomas that have hypermutated DNA owing to defects in the DNA mismatch repair pathway.

Hepatitis B (HBV) and C (HCV) viruses cause chronic inflammation which favors the appearance of hepatocarcinoma.

Tumor-specific antigens encoded by mutated genes were considered to be unsuitable for vaccines because they are different for every patient.

[11][12] For cervical carcinoma patients, long antigenic peptides derived from HPV proteins were used in cancer vaccines.

[13] Adoptive transfer involves either collecting from patients intratumoral or blood T cells, stimulate them in vitro against antigens present in the tumors and reinfuse them in large number into the patients, or using gene-modified T cells that recognize a tumor antigen.

Important tumor regressions were observed in patients treated with IL-2 and very large numbers (≥1010) of expanded TILs (tumor-infiltrating lymphocytes).

[14][15] Patients injected with expanded TILs directed against gp100 showed tumor regression but also significant adverse side effects such as uveitis.

Adoptive transfer of TILs can increase the survival of melanoma patients when it is used as an adjuvant therapy, i.e. after a surgery and before the appearance of metastases.

Clinical benefit from these treatments is positively correlated with the number of nonsynonymous mutations present in the tumors.

This suggests that the clinical benefit depends on T lymphocytes that recognize tumor-specific antigens encoded by mutated genes[18][19]