THE FREQUENCY OF MAJOR HISTOCOMPATIBILITY COMPLEX ANTIGEN ABNORMALITIES IN UROLOGICAL TUMORS AND THEIR CORRECTION BY GENE TRANSFECTION OR CYTOKINE STIMULATION

There is increasing evidence that loss of major histocompatibility com plex (MHC) antigens from tumors may be a factor in escape from immune surveillance. In an attempt to quantify this phenomenon in bladder tum ors, frozen sections were stained immunochemically and cell lines were tested in a radiobinding assay before and after treatment with interf eron gamma (IFN gamma) and after attempts to correct the defect by nor mal human leukocyte antigen (HLA) gene transfection. Study of 68 tumor sections with W6/32 antibody against monomorphic class I demonstrated that 42% had reduced or absent staining compared with the intensity o f stromal staining. Ten percent of cases bad complete absence with W6/ 32, all of which were also negative for beta 2-microglobulin (beta 2-m ) expression. Use of polymorphic antibodies for A2, A3, Bw4, and Bw6 i ncreased this frequency of defects to 73%. Study of 21 tumor cell line s with W6/32 demonstrated negative staining in five (23%) that could n ot be induced by IFN gamma and reduced staining in three (14%) that co uld be increased by IFN gamma, the remainder showing normal levels una ffected by IFN gamma. An additional six (28%) failed to express class II in response to IFN gamma, leading to an overall incidence of abnorm ality of 65%, in no case did cotransfection of one cell line with a de fect in one case transfection of beta 2-m gene into a class I negative line of fully assembled MHC class I antigens. It is concluded that th e majority of tumor cells demonstrate some form of MHC class I and II defects. The successful correction of MHC defect by beta 2-m transfect ion offers a well-defined subgroup of patients in whom it may be possi ble to test the effects of MHC gene therapy in the clinical setting an d study the relative strength of syngeneic versus allogeneic HLA antig ens for induction of bystander immunity.