Problems of Cancer Treatment. Part I. Theory of Treatment Based on Known Mechanisms of Anticancer Immunological Responses

Abstract

Summary: Various processes, taking place both in cells and in their environment, are linked to carcinogenesis. This paper aims at recalling the complex mechanisms of oncogenesis, with particular attention paid to responses of the immune system. In development of solid tumours, leukaemias and lymphomas several common stages can be noted. A neoplastic disease cannot be understood considering only phenomena of genetic mutations. Neoplastic cells are characterised by an extensive antigenic variability and resistance to apoptosis. The cells create around them a microenvironment which protects them from defensive activity of the host. In the paper we present the recognised mechanisms of anti-neoplastic defense as well as several elements allowing the solid tumours and leukaemias to escape from the immune surveillance. The generally accepted treatment of tumours aims at reducing numbers of tumour cells. Following resection of a tumour, radiotherapy or chemotherapy, the parallel or consecutive stage of treatment was found to involve an increase in number of clones of immune system cells. One of the ways in which the immune system can be activated involves autovaccination of the host with own neoplastic cells in an apoptosis. However, attempts of such a therapy frequently brought no expected results due to blocked activity of cytotoxic cells. Therefore, the subsequent stage in activation of the immune system should involve elimination of the tumor-mobilized blockade of the system. Attempts toward this aim include neutralization of the tumour-blocked cytotoxic properties of defensive cells, first of all T lymphocytes. The recognized mechanisms of blocking T cells activity in the PD-1/PD-L1 system or due to inhibition of activation by CTLA-4 molecule provided rationale for development of effective tumour immunotherapy approaches. Keywords