title: Synergy between CD8 T cells and Th1 or Th2 polarised CD4 T cells for adoptive immunotherapy of brain tumours.
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.
authors.affiliation: Centre of Oncology, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hoepner
authors.forename: Jacelyn M S
authors.initials: JM
authors.lastname: Loh
authors.forename: Cristina
authors.initials: C
authors.lastname: Riccadonna
authors.forename: Madiha
authors.initials: M
authors.lastname: Derouazi
authors.forename: Céline Yacoub
authors.initials: CY
authors.lastname: Maroun
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Dietrich
authors.forename: Paul R
authors.initials: PR
authors.lastname: Walker
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016764:Cell Polarity; D016207:Cytokines / Q000378:metabolism; D005260:Female; D016219:Immunotherapy, Adoptive; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D016201:Receptors, Lymphocyte Homing