Tumor infiltrating lymphocytes in ovarian cancer

Cancer Biol Ther. 2015;16(6):807-20. doi: 10.1080/15384047.2015.1040960. Epub 2015 Apr 20.

Abstract

The accumulation of tumor infiltrating lymphocytes (TILs) in ovarian cancer is prognostic for increased survival while increases in immunosuppressive regulatory T-cells (Tregs) are associated with poor outcomes. Approaches that bolster tumor-reactive TILs may limit tumor progression. However, identifying tumor-reactive TILs in ovarian cancer has been challenging, though adoptive TIL therapy in patients has been encouraging. Other forms of TIL immunomodulation remain under investigation including Treg depletion, antibody-based checkpoint modification, activation and amplification using dendritic cells, antigen presenting cells or IL-2 cytokine culture, adjuvant cytokine injections, and gene-engineered T-cells. Many approaches to TIL manipulation inhibit ovarian cancer progression in preclinical or clinical studies as monotherapy. Here, we review the impact of TILs in ovarian cancer and attempts to mobilize TILs to halt tumor progression. We conclude that effective TIL therapy for ovarian cancer is at the brink of translation and optimal TIL activity may require combined methodologies to deliver clinically-relevant treatment.

Keywords: CAR, chimeric antigen receptor; IDO, indoleamine 2,3-dioxygenase; TIL, tumor infiltrating lymphocyte; Tregs, regulatory T-cell; immunosuppression; immunotherapy; ovarian cancer; prognostic factors; regulatory T-cells; tumor infiltrating lymphocytes.

Publication types

  • Review

MeSH terms

  • Animals
  • Cancer Vaccines / immunology
  • Clinical Trials as Topic
  • Female
  • Humans
  • Immunomodulation
  • Immunotherapy, Adoptive
  • Lymphocyte Subsets / immunology*
  • Lymphocyte Subsets / metabolism
  • Lymphocyte Subsets / pathology
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Ovarian Neoplasms / immunology*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology*
  • Ovarian Neoplasms / therapy
  • Prognosis
  • Treatment Outcome
  • Tumor Microenvironment / immunology

Substances

  • Cancer Vaccines