The immunological response and post-treatment survival of DC-vaccinated melanoma patients are associated with increased Th1/Th17 and reduced Th3 cytokine responses

• Published in: Cancer Immunology, Immunotherapy Vol. 62; no. 4; pp. 761 - 772
• Main Authors: Durán-Aniotz, Claudia, Segal, Gabriela, Salazar, Lorena, Pereda, Cristián, Falcón, Cristián, Tempio, Fabián, Aguilera, Raquel, González, Rodrigo, Pérez, Claudio, Tittarelli, Andrés, Catalán, Diego, Nervi, Bruno, Larrondo, Milton, Salazar-Onfray, Flavio, López, Mercedes N.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.04.2013; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Antigens; Cancer Research; Cancer Vaccines - administration & dosage; Cancer Vaccines - immunology; Cytokines; Cytokines - immunology; Dendritic cells; Dendritic Cells - immunology; Female; Humans; Hypersensitivity, Delayed - immunology; Immunology; Immunotherapy; Immunotherapy, Adoptive - methods; Lymphatic system; Lymphocytes; Lymphoma; Male; Medical prognosis; Medicine; Medicine & Public Health; Melanoma; Melanoma - blood; Melanoma - immunology; Melanoma - therapy; Metastasis; Middle Aged; Oncology; Original; Original Article; Patients; Prostate cancer; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Regulatory - immunology; Th1 Cells - immunology; Th17 Cells - immunology; Tumors; Vaccines; Young Adult; Chile; Melanoma vaccine; Th17 lymphocytes; Dendritic cells; Regulatory T cells; Cancer immunotherapy
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-012-1377-3

Introduction Immunization with autologous dendritic cells (DCs) loaded with a heat shock-conditioned allogeneic melanoma cell lysate caused lysate-specific delayed type hypersensitivity (DTH) reactions in a number of patients. These responses correlated with a threefold prolonged long-term survival of DTH + with respect to DTH − unresponsive patients. Herein, we investigated whether the immunological reactions associated with prolonged survival were related to dissimilar cellular and cytokine responses in blood. Materials and methods Healthy donors and melanoma patient’s lymphocytes obtained from blood before and after vaccinations and from DTH biopsies were analyzed for T cell population distribution and cytokine release. Results/discussion Peripheral blood lymphocytes from melanoma patients have an increased proportion of Th3 (CD4 + TGF-β + ) regulatory T lymphocytes compared with healthy donors. Notably, DTH + patients showed a threefold reduction of Th3 cells compared with DTH − patients after DCs vaccine treatment. Furthermore, DCs vaccination resulted in a threefold augment of the proportion of IFN-γ releasing Th1 cells and in a twofold increase of the IL-17-producing Th17 population in DTH + with respect to DTH − patients. Increased Th1 and Th17 cell populations in both blood and DTH-derived tissues suggest that these profiles may be related to a more effective anti-melanoma response. Conclusions Our results indicate that increased proinflammatory cytokine profiles are related to detectable immunological responses in vivo (DTH) and to prolonged patient survival. Our study contributes to the understanding of immunological responses produced by DCs vaccines and to the identification of follow-up markers for patient outcome that may allow a closer individual monitoring of patients.