Synergy between CD8 T cells and Th1 or Th2 polarised CD4 T cells for adoptive immunotherapy of brain tumours

PLoS One. 2013 May 23;8(5):e63933. doi: 10.1371/journal.pone.0063933. Print 2013.

Abstract

The feasibility of cancer immunotherapy mediated by T lymphocytes is now a clinical reality. Indeed, many tumour associated antigens have been identified for cytotoxic CD8 T cells, which are believed to be key mediators of tumour rejection. However, for aggressive malignancies in specialised anatomic sites such as the brain, a limiting factor is suboptimal tumour infiltration by CD8 T cells. Here we take advantage of recent advances in T cell biology to differentially polarise CD4 T cells in order to explore their capacity to enhance immunotherapy. We used an adoptive cell therapy approach to work with clonal T cell populations of defined specificity. Th1 CD4 T cells preferentially homed to and accumulated within intracranial tumours compared with Th2 CD4 T cells. Moreover, tumour-antigen specific Th1 CD4 T cells enhanced CD8 T cell recruitment and function within the brain tumour bed. Survival of mice bearing intracranial tumours was significantly prolonged when CD4 and CD8 T cells were co-transferred. These results should encourage further definition of tumour antigens recognised by CD4 T cells, and exploitation of both CD4 and CD8 T cell subsets to optimise T cell therapy of cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / immunology
  • Brain Neoplasms / therapy*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Polarity
  • Cytokines / metabolism
  • Female
  • Immunotherapy, Adoptive*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neoplasm Transplantation
  • Receptors, Lymphocyte Homing / metabolism
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism

Substances

  • Cytokines
  • Receptors, Lymphocyte Homing

Grants and funding

This work was supported by a Swiss National Science Foundation (www.snf.ch/E/) Grant (31003A_120609) to PRW and by the Copley May Foundation to PYD. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.