Mesto imunoterapije pri zdravljenju raka Role of immunotherapy in cancer treatment

Abstract

Začetni poskusi zdravljena z imunoterapijo segajo v leto 1893. Skoraj stoletje kasneje pa so bila odobrena prva zdravila, ki jih štejemo med imunoterapijo, kot sta interferon in interlevkin. Vlogo imunskega sistema pri raku znanstveniki v zadnjih letih razlagajo s pomočjo protitumorskega imunskega cikla. V prvem koraku tega cikla pride do sproščanja tumorskih antigenov (neoantigenov), ki jih antigen predstavitvene celice spoznajo in ujamejo. V drugem koraku jih v bezgavkah predstavijo celicam T. Za aktivacijo in determinacijo celic T v smeri citotoksičnih T-celic je potreben še dodaten stimulatorni signal. Morebitni inhibitorni signali pa aktivacijo celic T zavirajo oz. preprečujejo čezmerno aktivacijo in avtoimunost. Aktivirane celice T po krvi potujejo v tumor. Tumorsko celico prepoznajo prek T-celičnega receptorja. S tem preide do uničenja tumorske celice. V sami tumorski stromi pa so lahko različni inhibitorni signali, ki delovanje citotoksičnih celic T onemogočijo. V prispevku so predstavljeni možni načini vplivanja na protitumorski imunski cikel in trenutno registrirana zdravila s področja imunoterapije.

Abstract (Eng)

The immunotherapy era began in 1893. Nearly a hundred years later, the first immunotherapy drugs were approved, for instance interferon and interleukin. The role of the immune system in cancer is best represented by the cancer-immunity cycle. In the first step of the cycle, tumor neo-antigens are released and, subsequently, captured by the antigen-presenting cells. In the second step, neo-antigens are presented to the T-cells in the lymph nodes. But additional co-stimulatory signals are needed for the priming and the activation of T cells. At that level, the potential inhibitory signals inhibit or prevent the hyperactivation of T cells and autoimmunity. The activated T cells migrate through circulation into the tumor tissue. A tumor cell is detected by a T-cell receptor. The result of this process is the so-called T-cell killing. A tumor stroma, however, can present different inhibitory signals that inhibit the function of cytotoxic T cells. The article presents the different ways of influencing the cancer-immunity cycle and the readily-approved immunotherapy drugs.