Restoration of expression of MHC class I molecule in Walker 256 tumor in growth dynamics in Brattleboro rats

Abstract

11 Establishing possible mechanisms influencing the growth and regression of malignant neoplasias is the key problem of modern experimental and clinical oncology. It is known that realization of these mecha� nisms includes both innate and adaptive immunity; natural killer cells (NK cells), macrophages, dendritic cells, various cytokines, and specific cytotoxic T cells. However, spontaneous regression of malignant tumors occurs very rarely, which is associated primarily with the “avoidance” of their recognition by the immune system. One of the causes of this phenomenon may be a low level of expression of the major histocompatibil� ity complex (MHC) class I antigens, which are required for presenting oncoantigens to cytotoxic T cells and/or disturbance of the regulatory mechanisms of their expression [1]. Our earlier study demonstrated complete regression of Walker 256 carcinosarcoma, a tumor that causes death of control WAG rats on day 25–27 after transplantation, in Brattleboro rats with genetically deficient synthesis of arginine–vasopressin (AVP) in the hypothalamus [2]. AVP deficiency is obviously a key condition that determines the regression of this tumor in Brattleboro rats. Apparently, the observed effect was not deter� mined by the rapid hormonal effect of AVP. According to published data, chronic systemic administration of AVP to Brattleboro rats normalizes the disturbed water–salt balance in them but has no effect on the increased activity of NK cells observed in these rats [3]. Since innate and adaptive immunity are related, it can be assumed that the enhancement of innate anti� tumor immunity in Brattleboro rats induces the devel� opment of specific immune reactions. This may be expressed as an increase in the efficiency of recogni� tion of transformed cells. The fact that a repeated transplantation of Walker 256 to Brattleboro rats did not result in tumor development allowed us to assume the involvement of adaptive immunity in the realiza� tion of this phenomenon.