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

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Abstract

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.

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Acknowledgments

Grants from the National Fund for Scientific and Technological Development (FONDECYT 1090243, 1090238, 3090044), the Fund for the Promotion of Scientific and Technological Development (FONDEF DO5I10366), and the Millennium Science Initiative from the Ministry supported this work for the Economy, Development and Tourism (P09/016-F).

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Authors and Affiliations

  1. Faculty of Medicine, Institute of Biomedical Sciences, University of Chile, 8380453, Santiago, Chile

    Claudia Durán-Aniotz, Gabriela Segal, Lorena Salazar, Cristián Pereda, Cristián Falcón, Fabián Tempio, Raquel Aguilera, Andrés Tittarelli, Diego Catalán, Flavio Salazar-Onfray & Mercedes N. López

  2. Millennium Institute on Immunology and Immunotherapy, University of Chile, 8380453, Santiago, Chile

    Fabián Tempio, Claudio Pérez, Andrés Tittarelli, Diego Catalán, Flavio Salazar-Onfray & Mercedes N. López

  3. Cell Therapy Laboratory, Blood Bank Service, University of Chile Clinical Hospital, 8380453, Santiago, Chile

    Rodrigo González, Claudio Pérez, Milton Larrondo & Mercedes N. López

  4. Department of Hematology and Oncology, Faculty of Medicine, Pontificial Catholic University of Chile, Santiago, Chile

    Bruno Nervi

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  1. Claudia Durán-Aniotz
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Correspondence to Mercedes N. López.

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Durán-Aniotz, C., Segal, G., Salazar, L. et al. The immunological response and post-treatment survival of DC-vaccinated melanoma patients are associated with increased Th1/Th17 and reduced Th3 cytokine responses. Cancer Immunol Immunother 62, 761–772 (2013). https://doi.org/10.1007/s00262-012-1377-3

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