4.4 Article

Tumor-specific CD8-positive T cell-mediated antitumor immunity is implicated in the antitumor effect of local hyperthermia

Journal

INTERNATIONAL JOURNAL OF HYPERTHERMIA
Volume 35, Issue 1, Pages 226-231

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/02656736.2018.1492027

Keywords

Hyperthermia; T cell; antitumor immunity; CD8; CTLA-4; E.G7-OVA

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Purpose: This study aimed to elucidate the contribution of T cell-mediated antitumor immunity in the antitumor effect of local hyperthermia (LH). Materials and methods: C57BL/6J mice were injected with the mouse lymphoma cell line, E.G7-OVA, in the right femur on day 0. LH was induced by immersing the right femur in a water bath at 42 degrees C for 60 min on day 7, followed by administration of anti-CD8 monoclonal antibodies (mAb) or anti-CTLA-4 mAb (days 8, 11, and 14). The effect of LH on tumor growth (TG) was assessed by measuring the duration until tumor volume reached 1000 mm(3) and survival time. Tumor-specific T cell responses were measured using enzyme-linked immunospot (ELISpot) assay. Results: TG with and without LH treatment was 9.0 +/- 9.6 and 7.0 +/- 1.6 days, respectively. TG was significantly slower with LH treatment (p = .01). The therapeutic effect of LH was mitigated by addition of anti-CD8 mAb (p < .05 for both TG and survival) compared with the untreated (control) group. Furthermore, addition of anti-CTLA-4 mAb did not significantly affect the therapeutic effect of LH. The ELISpot assay showed that the number of spots in the LH group (276.3 +/- 14.5) was significantly greater than in the control group (59.0 +/- 4.5, p < .001). Conclusion: CD8-positive T cell-mediated antitumor immunity significantly contributes to the antitumor effect of LH.

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