It has long been recognized that the immune system is able to recognize and destroy cancer cells, but although the immunological battle might slow the progression or spread of cancer, it’s usually the cancer that eventually wins the war.
Scientists have speculated that this may be because the immune response is not strong enough, or because it does not last long enough to have an effect. Hence the increasing efforts to develop cancer vaccines that induce, strengthen, and increase the duration of immunological attack against cancer cells. However a report published today in Cancer Research has helped to uncover part of the cancer’s battle-plan, and suggests new weapons for inclusion in the cancer vaccine arsenal.
In order to understand how tumors escape immunological attack, a team of investigators from the Lausanne Branch of the Ludwig Institute for Cancer Research (LICR), together with collaborators in Switzerland and Germany, analyzed the function of CD8 T cells that recognize a cancer-specific antigen. CD8 T cells are known as cytotoxic or ‘killer’ T cells because they cause the destruction of cells that display the antigen that the T cell recognizes; in this case, the melanoma-specific Melan-A/MART-1 antigen, which was discovered by the LICR. What they found, when they analyzed CD8 T cells taken from peripheral blood, subcutaneous metastases, and invaded lymph nodes from patients with metastatic melanoma, was that the tumor seemed to be somehow neutralizing the function of the cytotoxic T cells.
“We could clearly identify functional deficits in the cells isolated from the tumor sites,” explains Dr. Pedro Romero from the LICR’s Clinical Onco-Immunology Group, and a senior author of the study. “In contrast, T cells of the same antigen specificity, but isolated from peripheral blood, appeared functionally competent. This told us that something in the tumor environment was turning off the activity of the T cells, and suggested to us a mechanism through which the tumors might be escaping from the immune system.”