Splenic irradiation combined with tumor irradiation promotes T cell infiltration in the tumor microenvironment and helps in tumor control

Biochem Biophys Res Commun. 2019 Feb 26;510(1):156-162. doi: 10.1016/j.bbrc.2019.01.071. Epub 2019 Jan 22.

Abstract

Locally applied radiation to the tumor is reported to stimulate systemic immune response. During radiotherapy to the abdominal cancer, spleen often receives certain dose, though as an important immune organ, little is known about the impact of splenic irradiation (SI) on systemic immune and local tumor control. Through a mice model, we found that the combination of SI with tumor irradiation (TI) helped in local control. The analysis of the tumor infiltrating leucocytes demonstrated that SI plus TI brought more T cell aggregation in the tumor microenvironment (TME), which helped in tumor control. Increased T cell infiltration may be partly due to higher expression of T cell chemokine in the TME and more expression of CXCR3 on the T cells in the spleen after SI. SI produced more IL-1β in the spleen, IL-1β stimulated the expression of CXCR3 on the T cells, and enhanced their migration ability. Taken together, radiation to the spleen combined with TI helped in local control through promoting T cell infiltration, and may be a considerable means to enhance the immunomodulatory of radiotherapy.

Keywords: CXCR3; IL-1β; Splenic irradiation; Tumor infiltrating leucocytes; Tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / immunology
  • Chemokines / metabolism
  • Disease Models, Animal
  • Interleukin-1beta / metabolism
  • Lymphocytes, Tumor-Infiltrating / cytology
  • Lymphocytes, Tumor-Infiltrating / physiology
  • Mice
  • Neoplasms / prevention & control
  • Neoplasms / radiotherapy*
  • Receptors, CXCR3 / metabolism
  • Spleen / radiation effects*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • Treatment Outcome
  • Tumor Microenvironment / immunology

Substances

  • Chemokines
  • Cxcr3 protein, mouse
  • IL1B protein, mouse
  • Interleukin-1beta
  • Receptors, CXCR3