Generation of a dual-functioning antitumor immune response in the peritoneal cavity.
Tumor cell metastasis to the peritoneal cavity is observed in patients with tumors of peritoneal organs, particularly colon and ovarian tumors. Following release into the peritoneal cavity, tumor cells rapidly attach to the omentum, a tissue consisting of immune aggregates embedded in adipose tissue. Despite their proximity to potential immune effector cells, tumor cells grow aggressively on these immune aggregates. We hypothesized that activation of the immune aggregates would generate a productive antitumor immune response in the peritoneal cavity. We immunized mice i.p. with lethally irradiated cells of the colon adenocarcinoma line Colon38. Immunization resulted in temporary enlargement of immune aggregates, and after challenge with viable Colon38 cells, we did not detect tumor growth on the omentum. When Colon38-immunized mice were challenged with cells from the unrelated breast adenocarcinoma line E0771 or the melanoma line B16, these tumors also did not grow. The nonspecific response was long-lived and not present systemically, highlighting the uniqueness of the peritoneal cavity. Cellular depletions of immune subsets revealed that NK1.1(+) cells were essential in preventing growth of unrelated tumors, whereas NK1.1(+) cells and T cells were essential in preventing Colon38 tumor growth. Collectively, these data demonstrate that the peritoneal cavity has a unique environment capable of eliciting potent specific and nonspecific antitumor immune responses.
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York.
Abigail L
AL
Sedlacek
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York.
Scott A
SA
Gerber
Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
Troy D
TD
Randall
Department of Molecular Cell Biology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
Nico
N
van Rooijen
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York.
John G
JG
Frelinger
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York. Electronic address: edith_lord@urmc.rochester.edu.
Edith M
EM
Lord
D000818:Animals; D049109:Cell Proliferation; D006801:Humans; D007109:Immunity / Q000276:immunology*; D007114:Immunization; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009852:Omentum / Q000276:immunology / Q000473:pathology; D010529:Peritoneal Cavity / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D013601:T-Lymphocytes / Q000276:immunology