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PMID: 19997099 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

British journal of cancer ·Vol. 102 ·No. 1 ·2010-01-05 ·Pages 115-23

Liu WM, Fowler DW, Smith P, Dalgleish AG

Abstract

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. 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. 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. 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.

MeSH Terms
Animals Antigen Presentation/drug effects Antineoplastic Agents/administration & dosage,pharmacology Carcinoma/immunology,pathology Cell Line, Tumor/drug effects,immunology,transplantation Colonic Neoplasms/immunology,pathology Culture Media, Conditioned/pharmacology Cyclophosphamide/pharmacology Cytokines/metabolism,pharmacology Cytotoxicity, Immunologic/drug effects Dendritic Cells/drug effects,immunology Deoxycytidine/analogs & derivatives,pharmacology Female Gene Expression Regulation, Neoplastic/drug effects HLA-A1 Antigen/biosynthesis,genetics Humans Lymphocyte Activation/drug effects Male Mice Mice, Nude Organoplatinum Compounds/pharmacology Oxaliplatin Premedication T-Lymphocytes, Cytotoxic/drug effects,immunology
Chemicals
Antineoplastic Agents Culture Media, Conditioned Cytokines HLA-A1 Antigen Organoplatinum Compounds Oxaliplatin Deoxycytidine Cyclophosphamide gemcitabine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Liu W M
Section of Oncology, Division of Cellular and Molecular Medicine, St George's University of London, London, UK. [email protected]
Fowler D W
Smith P
Dalgleish A G
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Article Info
Journal
British journal of cancer
Abbr.
Br J Cancer
ISSN
1532-1827
Published
2010-01-05
Epub
2009-00-08
Pages
115-23
Language
English
Region
England
NLM ID
0370635
PMCID
PMC2813751
Subset
IM
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