title: Tumor macrophages as a target for Capsaicin mediated immunotherapy.
abstract: Tumor microenvironment contributes to a large extent for failure of immunological destruction of antigenic tumors. Most solid tumors adapt to the microenvironment and escape the host immune system. The dramatic and systemic effectiveness of neuro-immune ligand Capsaicin (CP) in regression of established solid tumors led us to investigate its immunomodulatory role in tumor microenvironment. In this report we demonstrate that CP induced tumor cell apoptosis leads to increased sensitization of the surrounding stroma manifested by enhanced antigen presentation by stromal macrophages and its destruction by tumor specific T-cells. Further, CP injection alters the tumor microenvironment with regards to tumor-infiltrating Treg cells as well as the cytokine milieu at the tumor site. Our data collectively demonstrates that injection of CP sets in motion, a cascade of several independent innate and adaptive immunological events initiated at the tumor environment.
authors.affiliation: Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, MC1601, Farmington, CT 06030-1601, United States.
authors.forename: Amiya K
authors.initials: AK
authors.lastname: Ghosh
authors.forename: Sreyashi
authors.initials: S
authors.lastname: Basu
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D039481:CD11b Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes; D002211:Capsaicin / Q000276:immunology / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007155:Immunologic Factors / Q000494:pharmacology; D007167:Immunotherapy / Q000379:methods*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D017154:Stromal Cells / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D059016:Tumor Microenvironment / Q000187:drug effects; D000093542:Gemcitabine
chemical_list: D000951:Antigens, Neoplasm; D039481:CD11b Antigen; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C508018:Il2ra protein, mouse; D007155:Immunologic Factors; D053645:Interleukin-2 Receptor alpha Subunit; D003841:Deoxycytidine; D002211:Capsaicin; D000093542:Gemcitabine