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


CONCLUSIONS
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.
Liu
W M
WM
Section of Oncology, Division of Cellular and Molecular Medicine, St George's University of London, London, UK. w.liu@sgul.ac.uk
Fowler
D W
DW
Smith
P
P
Dalgleish
A G
AG
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002277:Carcinoma / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000276:immunology / Q000637:transplantation; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D015788:HLA-A1 Antigen / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D011292:Premedication; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D017077:Culture Media, Conditioned; D016207:Cytokines; D015788:HLA-A1 Antigen; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D003520:Cyclophosphamide; D000093542:Gemcitabine