Effect of Human Leukocyte Antigen Class I Expression of Tumor Cells on Outcome of Intravesical Instillation of Bacillus Calmette-Guerin Immunotherapy for Bladder Cancer

Abstract

Purpose: Various immune systems play important roles in the clinical efficacy of intravesical Bacillus Calmette-Guerin (BCG) instillation for bladder cancer. However, human leukocyte antigen (HLA) class I molecules on tumor cells and various immune system cells infiltrating to/around the tumor have not been evaluated, although many prognostic factors, including clinical, pathologic, and molecular ones, have been investigated. The aim of this study was to determine immunologic prognostic factors of BCG immunotherapy for bladder cancer. Experimental Design: Immunohistochemical staining for HLA class I, CD4, CD8, CD20, CD68, TIA-1, S-100, and FOXP3 was carried out on specimens from 30 patients who underwent BCG immunotherapy from whom both pretreatment and posttreatment specimens were obtained.We did univariate and multivariate analyses of factors affecting recurrence-free survival. The positive, weakly positive, and negative groups of cells that infiltrated to/around the tumor were compared with recurrence-free survival using the Kaplan-Meier method and log-rank test. Results: HLA class I was a significant prognostic factor both in univariate and multivariate analyses. The 5-year recurrence-free survivals of the patients with HLA class I^positive tumors and those with HLA class I^negative tumors were 55.7% and 19.1%, respectively (P = 0.019). There was a significant association between infiltration of CD8, CD20, and CD68-positive cells after BCG therapy and therapeutic effects. Conclusions: Our data show that expression of HLA class I molecules on tumor cells contributes significantly to the therapeutic effect of BCG immunotherapy for bladder cancer. It is suggested that CTLs may be one of main effectors in this therapy.

Intravesical ALT-803 and BCG Treatment Reduces Tumor Burden in a Carcinogen Induced Bladder Cancer Rat Model; a Role for Cytokine Production and NK Cell Expansion

“…This was associated with an antitumor response and a marked increase in infiltrating NK cells within the bladder along with secretion of factors involved in inflammatory and immune responses. Among the locally elevated immune factors triggered by the combination of ALT-803 and BCG treatment within the bladder included IL-1α and IL-1β, which are both secreted by activated macrophages and neutrophils and are known to play major roles in the initiation and regulation of inflammation [41]. BCG has previously been linked to the up-regulation of IL-1α and IL-1β [42].…”

Immune Escape Mechanisms as a Guide for Cancer Immunotherapy

“…More recently, this knowledge has been underscored by findings showing that MHC class I and II molecules can be used as independent prognostic factors for colorectal cancer (21) and for predicting the efficacy of immunotherapy in bladder cancer (22) and chemotherapy in ovarian cancer (23). Together, we believe that this data strongly argues a role for MHC class I/II testing of tumor tissue as a measure of antigenicity in order to identify patients who are most likely to benefit from T cell immunotherapy.…”

Clonal diversity of cytotoxic T lymphocytes that recognize autologous oral squamous cell carcinoma

“…Therefore, vaccination therapy with antigenic peptides of OSCC patients might have enough potential to remove cancer cells. Recently we reported that HLA-class I downregulation was one of the factors for poor prognoses in bladder cancer and osteosarcoma [26,27]. These findings also sup- port the idea that immunoreaction against cancer cells has sufficient competency for cancer rejection.…”