Using chemo-drugs or irradiation to break immune tolerance and facilitate immunotherapy in solid cancer

Cell Immunol. 2015 Mar;294(1):54-9. doi: 10.1016/j.cellimm.2015.02.003. Epub 2015 Feb 10.

Abstract

The immunity is dual host-protective and tumor-promoting in cancer development and progression. Many immune suppressive cells and cytokines in microenvironment can prevent cytotoxic T lymphocytes (CTL) and natural killer cells (NK) from killing tumor cells. Chemotherapy drugs and irradiation have been reported helpful in breaking immune tolerance and creating microenvironment for adoptive cell therapy. Low-dose cyclophosphamide or gemcitabine therapy can selectively deplete T regulatory cells (Treg). Paclitaxel can alter cytokine network at the tumor site, and 5-fluorouracil shows a pronounced effect on myeloid-derived suppressor cells (MDSC) depletion. Local tumor irradiation and total body irradiation (TBI) can also affect tumor microenvironment and facilitate immunotherapy. In this review, we summarize the particular effects of these agents and methods on immunomodulation, as well as their potential values in immunotherapy. The combination with immunotherapy represents a novel therapeutic strategy.

Keywords: Chemo-drug; Immune tolerance; Immunotherapy; Irradiation; Low-dose.

Publication types

  • Review

MeSH terms

  • Antimetabolites, Antineoplastic / therapeutic use
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Cyclophosphamide / therapeutic use
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Fluorouracil / therapeutic use
  • Gemcitabine
  • Humans
  • Immunotherapy / methods*
  • Killer Cells, Natural / immunology
  • Neoplasms / drug therapy
  • Neoplasms / immunology*
  • Neoplasms / radiotherapy
  • Paclitaxel / therapeutic use
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Tumor Escape / drug effects*
  • Tumor Escape / immunology
  • Tumor Escape / radiation effects*
  • Tumor Microenvironment / immunology

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents, Alkylating
  • Antineoplastic Agents, Phytogenic
  • Deoxycytidine
  • Cyclophosphamide
  • Paclitaxel
  • Fluorouracil
  • Gemcitabine