BIOLOGICAL SIGNIFICANCE OF BETA hCG, HLA AND OTHER MEMBRANE ANTIGEN EXPRESSION ON BLADDER TUMOURS AND THEIR RELATIONSHIP TO TUMOUR INFILTRATING LYMPHOCYTES (TIL)

Abstract

SUMMARY Expression of beta human chorionic gonadotropin (βhCG) by bladder tumours has been shown to be associated with increased metastases and resistance to treatment with radiotherapy and chemotherapy. Preliminary results from typing frozen tumours using monoclonal antibodies against HLA determinants show reduced or lost expression of one or more antigens in two thirds of patients studied with a trend for more malignant behaviour and inability to generate tumour infiltrating lymphocyte expression using Interleukin‐2 in those patients whose tumours demonstrate loss. In this series βhCG expression was only seen in a subgroup of those demonstrating loss of HLA antigen expression. Studies of βhCG secreting bladder cancer cell lines showed that it was possible to induce class II HLA antigen expression with gamma Interferon, and that this treatment but not alpha Interferon reduced βhCG production by the cell line.

Silencing of the TGF-β1 Gene Increases the Immunogenicity of Cells From Human Ovarian Carcinoma

“…42-46 The efficacy of vaccination may be further improved by engineering the tumor cells to engage immunostimulatory molecules such as GM-CSF, CD40, CD80, CD83, CD137 etc. 4-6, 47-49 However, to achieve therapeutic efficacy against tumors which are larger than a few mm in diameter, the powerful immunosuppressive mechanisms at tumor sites need to be overcome.…”

Inhibition of TGFβ1 Makes Nonimmunogenic Tumor Cells Effective for Therapeutic Vaccination

“…Further work is needed to find out whether the same is true when using dendritic cells that have been pulsed 11 or transfected 9 with tumor material. We hypothesize that the situation may be similar for other members of the TGFb family and other tumor-produced immunosuppressive molecules including hCG 40 and B7-H-1. 41 We further hypothesize that the efficacy of vaccination can be improved by transfecting tumor cells whose production of immunosuppressive factors has been inhibited to also engage immunostimulatory signals, for example, via CD80, 14 anti-CD137scFv, 16 CD83, 17 or granulocyte-macrophage colony-stimulating factor.…”

Correlation between class I antigen expression and the ability to generate tumour infiltrating lymphocytes from bladder tumour biopsies

“…Preliminary information from our own work has demonstrated more frequent reactivity of anti-HPV16 E7 antibody with superficial than invasive tumour (Oliver, 1989). As loss of HLA class I is also more frequent in invasive tumours (Nouri et al, 1990), it is possible that HPV antigen in association with appropriate HLA could be explored as possible vaccine for cancer patients (Anon, 1989).…”

“…One possible factor explaining this has come from the recent studies in bladder cancer. These have demonstrated that more than 50% of bladder tumours have variable degrees of polymorphic or monomorphic HLA class I antigen loss (Nouri et al, 1990) as an immune escape mechanism in association with P h C G expression (Oliver et al, 1989). This paper set out to study generation of TILs from bladder cancer biopsies and investigated the influence of HLA class I expression on the ability to generate TILs.…”