Anti-tumor characteristics of radiation-induced tumor-infiltrating neutrophils
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POSTER PRESENTATION
Open Access
Anti-tumor characteristics of radiation-induced tumor-infiltrating neutrophils Tsuguhide Takeshima*, Ellen Vitetta, Raquibul Hannan From Society for Immunotherapy of Cancer 29th Annual Meeting National Harbor, MD, USA. 6-9 November 2014
It is now evident that interactions between tumor cells and host tissue stoma play a key role in tumor progression. Understanding the composition of the stromal cells in the tumor microenvironment immediately after tumor irradiation might be an important first step in understanding immunomodulation by radiation therapy. To explore this, we harvested tumor masses, draining lymph nodes (DLNs), spleens, and peripheral blood mononuclear cells (PBMCs) between 6h-96h after a single 15 Gy dose of focused irradiation of RM-9 mouse prostate tumor grafts growing in the hind leg of syngeneic C57BL/6 mice. Subpopulations of lymphocytes and granulocytes (CD4+, CD8+, CD4+CD25+, CD11c+, CD11b+Gr-1+mid, and CD11b+Gr-1+high cells) were analyzed by flow cytometry. We have previously reported that there is an infiltration of CD11b+Gr-1 +high neutrophils into the tumor that reached a peak within 24-48 h after tumor irradiation (Fig. 1A). To investigate the generality of this phenomenon, the lung cancer cell line LLC and the breast cancer cell line 4T1 was implanted in their respective syngeneic hosts; C57BL/6 and BALB/c mice. In both models neutrophilic infiltration was observed at 24-48h after tumor irradiation (Fig. 1B, C). To investigate the effect of neutrophils on tumor growth, we compared the tumor sizes in mice treated with the neutrophil-depleting anti-Ly-6G mAb to those of mice treated with an isotype-matched control antibody. The therapeutic effect of irradiation was significantly attenuated in all three tumor models when neutrophils were depleted (Fig. 2). To evaluate the impact of the neutrophilic infiltration on tumor-specific immune responses, we generated OVA gene-transfected RM-9 and RM-9-OVA-tumor-bearing mice for detecting
Figure 1 CD11b+Gb-1+ cells increase in tumor tissue 24 hour after tumor irradiation. RM-9- (a) LLC- (B) and 4T1- (C) bearing mice (n = 5) were sacrificed at different times after 15 Gy irradiation to the tumor on the left hind leg and the tumor tissues were analyzed for neutrophils (CD11b+Gr-1+ cells) by flow cytometry. The results show a significant increase in neutrophilic infilitration 24-48h after tumor irradiation.
Univ. of Texas Southwestern Medical Center, Dallas, TX, USA © 2014 Takeshima et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Takeshima et al. Journal for ImmunoTherapy of Canc
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