Tahtinen , S , Kaikkonen , S , Merisalo-Soikkeli , M , Gronberg-Vaha-Koskela , S , Kanerva , A , Parviainen , S , Vaha-Koskela , M & Hemminki , A 2015 , ' Favorable Alteration of Tumor Microenvironment by Immunomodulatory Cytokines for Efficient T-Cell Therapy in Solid Tumors ' , PLoS One , vol. 10 , no. 6 , 0131242 . https://doi.org/10.1371/journal.pone.0131242
Title: | Favorable Alteration of Tumor Microenvironment by Immunomodulatory Cytokines for Efficient T-Cell Therapy in Solid Tumors |
Author: | Tahtinen, Siri; Kaikkonen, Saija; Merisalo-Soikkeli, Maiju; Gronberg-Vaha-Koskela, Susanna; Kanerva, Anna; Parviainen, Suvi; Vaha-Koskela, Markus; Hemminki, Akseli |
Contributor organization: | Medicum Department of Pathology Transplantation Laboratory Department of Obstetrics and Gynecology Clinicum Department of Oncology |
Date: | 2015-06-24 |
Language: | eng |
Number of pages: | 20 |
Belongs to series: | PLoS One |
ISSN: | 1932-6203 |
DOI: | https://doi.org/10.1371/journal.pone.0131242 |
URI: | http://hdl.handle.net/10138/160383 |
Abstract: | Unfavorable ratios between the number and activation status of effector and suppressor immune cells infiltrating the tumor contribute to resistance of solid tumors to T-cell based therapies. Here, we studied the capacity of FDA and EMA approved recombinant cytokines to manipulate this balance in favor of efficient anti-tumor responses in B16. OVA melanoma bearing C57BL/6 mice. Intratumoral administration of IFN-alpha 2, IFN-gamma, TNF-alpha, and IL-2 significantly enhanced the anti-tumor effect of ovalbumin-specific CD8+ T-cell (OT-I) therapy, whereas GM-CSF increased tumor growth in association with an increase in immunosuppressive cell populations. None of the cytokines augmented tumor trafficking of OT-I cells significantly, but injections of IFN-alpha 2, IFN-gamma and IL-2 increased intratumoral cytokine secretion and recruitment of endogenous immune cells capable of stimulating T-cells, such as natural killer and maturated CD11c+ antigen-presenting cells. Moreover, IFN-alpha 2 and IL-2 increased the levels of activated tumor-infiltrating CD8+ T-cells concomitant with reduction in the CD8+ T-cell expression of anergy markers CTLA-4 and PD-1. In conclusion, intratumoral administration of IFN-alpha 2, IFN-gamma and IL-2 can lead to immune sensitization of the established tumor, whereas GM-CSF may contribute to tumor-associated immunosuppression. The results described here provide rationale for including local administration of immunostimulatory cytokines into T-cell therapy regimens. One appealing embodiment of this would be vectored delivery which could be advantageous over direct injection of recombinant molecules with regard to efficacy, cost, persistence and convenience. |
Subject: |
COLONY-STIMULATING FACTOR
METASTATIC MELANOMA DENDRITIC CELLS IN-VIVO CANCER IMMUNOTHERAPY ANTIGEN RESPONSES IL-2 PROGRESSION 3111 Biomedicine |
Peer reviewed: | Yes |
Rights: | cc_by |
Usage restriction: | openAccess |
Self-archived version: | publishedVersion |
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