Importance of MHC antigen expression on solid tumors in the in vitro interaction with autologous blood lymphocytes

Abstract

In 54 patients with lung and 14 with ovarian carcinomas the quantitative variations of the major histocompatibility complex (MHC)-determined class I and class II antigens of the tumor cells were related to their in vitro interaction with blood lymphocytes, to the lymphoid infiltration of the tumors, and to the metastatic state of the disease. The tumor cell-lymphocyte interaction was measured by the proliferative response in mixed lymphocyte tumor cell culture and by the cytotoxic activity of the lymphocytes. The results showed that (1) none of the 23 tumors from patients with disseminated disease were lysed; (2) class I-negative tumors were not damaged; (3) lymphoid infiltration was present in a higher proportion of class II-positive tumors; and (4) both MHC-positive and -negative tumors were found among the disseminated tumors. The requirement of class I expression in the lytic interaction substantiates our earlier conclusion concerning the cytotoxic T lymphocyte nature of lymphocyte-mediated auto-tumor lysis. The lack of auto-tumor lysis in patients with metastases suggests impairment of lymphocyte function in advanced stages of the disease.

Aberrantly expressed cytokeratin 1, a tumor-associated autoantigen in papillary thyroid carcinoma

“…In PTC, the presence of autoantibodies to cytokeratin 1 therefore suggests the development of an autoimmune response, which infers Th-cell activation. (Topalian, 1994;Vanky and Klein, 1991). The finding of cytokeratin 1 antibodies in HT but not GD serum corroborates a cytolytic mechanism in PTC and HT, producing autoantibodies primarily to intracellular antigens.…”

Potentiation of the efficacy of murine L1210 leukemia vaccine by a novel immunostimulator 7-thia-8-oxoguanosine: Increased survival after immunization with vaccine plus 7-thia-8-oxoguanosine

“…The majority of cytotoxic T lymphocytes (CTL) recognize tumor cells in association with class I molecules encoded by the MHC. Several types of tumor cells either do not express, or display greatly reduced levels of class I MHC antigens on their surface [1,20,29,30]. It was shown that expression of class I molecules can be induced on the surface of different tumor cells by IFN and TNFc~ treatment [30].…”

“…The majority of tumors with different tissue origins lack or express only low levels of class I antigens. Thus, they may not be able to induce an effective immune response [1,28,29]. It was shown recently that treatment of tumor cells with interferon (IFN) and tumor necrosis factor (x (TNFc0 induced the expression of MHC class I antigens on tumor cells [30].…”

“…It has been shown that the presence of MHC antigens, especially class I, on the tumor cell surface is critical for eliciting a potent immune response against malignant cells [1,29]. The majority of tumors with different tissue origins lack or express only low levels of class I antigens.…”

Application of isoelectric focusing for studies of major histocompatibility complex class I antigen expression on human carcinomas and sarcomas

“…In our series of experiments human tumours that lacked or had low amounts of MHC class I antigens were not lysed by, and did not stimulate the autologous blood lymphocytes. Tumours that were recognized in vitro by the lymphocytes expressed both class I antigens and the intercellular adhesion molecule I (ICAM-I) [24][25][26].Offprint requests to: E Vänky, Department of Tumor Biology, Karolinska Institute, 104 01 Stockholm 60500, Sweden Detailed analysis of HLA allele expression on tumour cells is not possible with the conventional lymphocyte typing method. The use of monoclonal antibodies (mAbs) on tissue sections has revealed selective loss of certain alleles [12,13,20].…”