title: Induction of specific cellular and humoral responses against renal cell carcinoma after combination therapy with cryoablation and granulocyte-macrophage colony stimulating factor: a pilot study.
abstract: Cryotherapy offers a minimally invasive treatment option for the management of both irresectable and localized prostate, liver, pulmonary, and renal tumors. The antineoplastic effects of cryotherapy are mediated by direct tumor lysis and by indirect effects, such as intracellular dehydration, pH changes, and microvascular damage resulting in ischemic necrosis. In this study, we investigated whether percutaneous cryoablation of lung metastasis from renal cell carcinoma (RCC) in combination with aerosolized granulocyte-macrophage colony stimulating factor can induce systemic cellular and humoral immune responses in 6 patients with RCC. Peripheral blood mononuclear cells (PBMCs) were sequentially studied up to 63 days post cryoimmunotherapy (CI). PBMC from pre and post CI were phenotyped for lymphocyte subsets and tested for cytotoxicity and interferon-γ EliSpots directed at RCC cells. Humoral responses were measured by in vitro antibody synthesis assay directed at RCC cells. The immune monitoring data showed that CI induced tumor specific cytotoxic T lymphocyte, specific in vitro antitumor antibody responses, and enhanced Th1 cytokine production in 4 of 6 patients. More importantly, the magnitude of cellular and humoral antitumor response seems to be associated with clinical responses. These pilot data show that CI can induce robust and brisk cellular and humoral immune responses in patients with metastatic RCC, but requires further evaluation in optimized protocols.
authors.affiliation: Department of Oncology, Wayne State University, Karmanos Cancer Institute, Detroit, MI, USA. thakur@karmanos.org
authors.forename: Archana
authors.initials: A
authors.lastname: Thakur
authors.forename: Peter
authors.initials: P
authors.lastname: Littrup
authors.forename: Elyse N
authors.initials: EN
authors.lastname: Paul
authors.forename: Barbara
authors.initials: B
authors.lastname: Adam
authors.forename: Lance K
authors.initials: LK
authors.lastname: Heilbrun
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Lum
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell; D003131:Combined Modality Therapy; D003452:Cryosurgery; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D007371:Interferon-gamma / Q000008:administration & dosage / Q000276:immunology; D007680:Kidney Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology / Q000556:secondary / Q000601:surgery; D016131:Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D008297:Male; D011994:Recombinant Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor