Pre-treatment with chemotherapy can enhance the antigenicity and immunogenicity of tumours by promoting adaptive immune responses

Br J Cancer. 2010 Jan 5;102(1):115-23. doi: 10.1038/sj.bjc.6605465. Epub 2009 Dec 8.

Abstract

Background: Some cancer patients are immuno-compromised, and it has been long felt that immune-intervention is not compatible with standard chemotherapies. However, increasing evidence suggests that standard chemotherapy drugs may stimulate beneficial changes in both the immune system and tumour.

Methods: We have assessed the expression of human leucocyte antigen class 1 (HLA1) on tumour cells before and after chemotherapy agents (cyclophosphamide, oxaliplatin or gemcitabine). In addition, we show that chemotherapy-stressed tumour cells may release cytokines that enhance the interactions between dendritic cells (DCs) and T cells into growth media.

Results: Here we report that some chemotherapy agents can increase HLA1 expression in tumour cells, even when expression is low. Increases were associated with killing by cytotoxic T cells, which were negated by HLA1-blockade. Furthermore, T-cell function, as indicated by increased proliferation, was enhanced as supernatants derived from tumours treated with chemotherapy augmented DC-maturation and function.

Conclusion: There is evidence that a facet of immune surveillance can be restored by appropriate chemotherapy agents. Also, tumours exposed to some chemotherapy may secrete cytokines that can mature DCs, which ultimately enhances T-cell responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / drug effects*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Carcinoma / immunology*
  • Carcinoma / pathology
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / immunology
  • Cell Line, Tumor / transplantation
  • Colonic Neoplasms / immunology*
  • Colonic Neoplasms / pathology
  • Culture Media, Conditioned / pharmacology
  • Cyclophosphamide / pharmacology
  • Cytokines / metabolism
  • Cytokines / pharmacology
  • Cytotoxicity, Immunologic / drug effects*
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • HLA-A1 Antigen / biosynthesis*
  • HLA-A1 Antigen / genetics
  • Humans
  • Lymphocyte Activation / drug effects*
  • Male
  • Mice
  • Mice, Nude
  • Organoplatinum Compounds / pharmacology
  • Oxaliplatin
  • Premedication
  • T-Lymphocytes, Cytotoxic / drug effects*
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Antineoplastic Agents
  • Culture Media, Conditioned
  • Cytokines
  • HLA-A1 Antigen
  • Organoplatinum Compounds
  • Oxaliplatin
  • Deoxycytidine
  • Cyclophosphamide
  • gemcitabine