title: Surgical removal of primary tumor reverses tumor-induced immunosuppression despite the presence of metastatic disease.
abstract: Immunotherapy is a promising approach for the management of malignancies. It may be particularly useful for tumors that do not respond to conventional therapies, such as many metastatic cancers. The efficacy of immunotherapy will depend on many factors, one of which is the immunocompetence of the host. Patients with large primary tumors frequently are immunosuppressed, making them poor candidates for immunotherapy. Although a few studies have reported that surgical removal of primary tumor reverses immunosuppression, it is not known whether metastatic disease in postsurgery patients inhibits this recovery. To determine the role of metastatic disease, we examined tumor-free mice versus mice with primary tumor and metastatic disease versus mice whose primary tumors were removed surgically but who had metastatic disease. We have used the mouse 4T1 mammary carcinoma, a BALB/c-derived transplantable tumor that shares many characteristics with human breast cancer and is an established model for spontaneous, metastatic cancer. Cell-mediated and humoral adaptive immunity, as measured by rejection of allogeneic tumor, antigen-specific T-cell proliferation, and antigen-specific antibody responses, was suppressed in 4T1-bearing nonsurgery mice relative to tumor-free mice. Surgical removal of primary tumor resulted in rebounding of antibody and cell-mediated responses, even in mice with metastatic disease. Macrophage activity, as measured by lipopolysaccharide responsiveness, and dendritic cell function, as measured by nominal and alloantigen presentation, were not suppressed in tumor-bearing mice. Therefore, the presence of primary tumor suppresses T-cell and antibody responses; however, surgical removal of primary tumor restores immunocompetence even when disseminated metastatic disease is present.
authors.affiliation: Department of Biological Sciences, University of Maryland-Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
authors.forename: Erika A
authors.initials: EA
authors.lastname: Danna
authors.forename: Pratima
authors.initials: P
authors.lastname: Sinha
authors.forename: Mileka
authors.initials: M
authors.lastname: Gilbert
authors.forename: Virginia K
authors.initials: VK
authors.lastname: Clements
authors.forename: Beth A
authors.initials: BA
authors.lastname: Pulaski
authors.forename: Suzanne
authors.initials: S
authors.lastname: Ostrand-Rosenberg
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D007114:Immunization; D007165:Immunosuppression Therapy; D008070:Lipopolysaccharides / Q000494:pharmacology; D008175:Lung Neoplasms / Q000276:immunology* / Q000556:secondary; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D008546:Melanoma, Experimental / Q000276:immunology* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009113:Muramidase / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D008070:Lipopolysaccharides; C421864:hen egg lysozyme; D009113:Muramidase