CIITA-induced MHC class II expression in mammary adenocarcinoma leads to a Th1 polarization of the tumor microenvironment, tumor rejection, and specific antitumor memory

Lorenzo Mortara, Patrizia Castellani, Raffaella Meazza, Giovanna Tosi, Andrea De Lerma Barbaro, Francesco A. Procopio, Alberto Comes, Luciano Zardi, Silvano Ferrini, Roberto S. Accolla

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: We have shown previously that the MHC class II-negative murine TS/A adenocarcinoma is rejected in vivo if induced to express MHC class II molecules by transfection of the MHC class II transactivator CIITA. In this study, we explored the immunologic basis of tumor rejection and the correlation between histopathology of tumor tissue and immune rejection. Experimental Design: Stable TS/A-CIITA transfectants were generated and injected into mice. In vivo cell depletion, immunohistochemistry of tumor tissues, and immune functional assays were done to assess the cellular and immunologic basis of rejection. Results: Ninety-two percent of mice injected with TS/A-CIITA rejected the tumor and were completely resistant to challenge with parental TS/A. Only CD4+ and CD8+ cells were required for rejection. The tumor microenvironment in TS/A-CIITA-injected mice changed dramatically when compared with the TS/A parental-injected mice. Rapid infiltration with CD4+ T cells followed by dendritic cells, CD8+ T cells, and granulocytes was observed. Importantly,TS/A-CIITA cells could act as antigen-presenting cells because they process and present nominal antigens to CD4+ T cells. Tumor-specific CD4+ T cells of TS/A-CIITA-injected mice had the functional characteristics of Th1 cells and produced IFN-γ and this was relevant for generation and maintenance of protective antitumor response, because IFN-γ knockout mice were no longer rejecting TS/A-CIITA tumor cells. Conclusion: CIITA-dependent MHC class II expression confers to TS/A tumor cells the capacity to act as a protective vaccine against the tumor by triggering tumor antigen presentation to T helper cells, antitumor polarization of cellular and soluble components of the tumor microenvironment, and establishment of antitumor immune memory.

Original languageEnglish
Pages (from-to)3435-3443
Number of pages9
JournalClinical Cancer Research
Volume12
Issue number11 I
DOIs
Publication statusPublished - Jun 1 2006

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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