Partial, but not complete, tumor-debulking surgery promotes protective antitumor memory when combined with chemotherapy and adjuvant immunotherapy.
Resection alone is rarely curative for advanced tumors, but the outcome generally improves with adjuvant therapy. We have previously shown that a combination of traditional chemotherapy (gemcitabine) and immunotherapy (anti-CD40/FGK-45) without surgery is synergistic and can lead to long-term cure when applied to small tumors. Such cured animals have immunologic memory and are protected from rechallenge. Here we investigate the effectiveness of combination chemotherapy and immunotherapy after partial or complete surgical debulking of large tumors. We found that complete resection followed by combination chemotherapy/immunotherapy led to a high rate of cure (>80%) but failed to induce a long-term, tumor-specific memory. Partial debulking followed by combination therapy elicited the same proportion of cured animals but in contrast to complete resection, a memory response was invoked. We postulate that chemotherapy induced apoptosis of the residual tumor cells following incomplete resection is absolutely required for the induction of long-term immunologic memory.
Broomfield
Steve
S
School of Medicine and Pharmacology and Western Australian Institute for Medical Research, Sir Charles Gairdner Hospital, University of Western Australia, Nedlands, Perth, Australia.
Currie
Andrew
A
van der Most
Robbert G
RG
Brown
Matthew
M
van Bruggen
Ivonne
I
Robinson
Bruce W S
BW
Lake
Richard A
RA
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D019013:CD40 Antigens / Q000276:immunology*; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007116:Immunization, Passive / Q000379:methods; D007156:Immunologic Memory; D008654:Mesothelioma / Q000188:drug therapy / Q000276:immunology* / Q000601:surgery / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D000093542:Gemcitabine
D000906:Antibodies; D000964:Antimetabolites, Antineoplastic; D019013:CD40 Antigens; D003841:Deoxycytidine; D000093542:Gemcitabine