Ken Ando1, Yoshiyuki Suzuki1,2, Takuya Kaminuma1, Yuya Yoshimoto1, Takahiro Oike1, Noriyuki Okonogi1,3, Hiro Sato1, Tomoaki Tamaki2, Shin-Ei Noda1,4, Kosaku Mimura5,6, Takashi Nakano1. 1. a Department of Radiation Oncology , Gunma University Graduate School of Medicine , Maebashi , Japan. 2. b Department of Radiation Oncology , Fukushima Medical University , Fukushima City , Japan. 3. c National Institute of Radiological Sciences Hospital , National Institutes for Quantum and Radiological Science and Technology , Chiba , Japan. 4. d Department of Radiation Oncology , Saitama Medical University, International Medical Center , Hidaka , Japan. 5. e Department of Progressive DOHaD Research , Fukushima Medical University , Fukushima City , Japan. 6. f Department of Gastrointestinal Tract Surgery , Fukushima Medical University , Fukushima City , Japan.
Abstract
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 °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 mm3 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.
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 mouselymphoma 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 °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 mm3 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.
Entities:
Keywords:
CD8; CTLA-4; E.G7-OVA; Hyperthermia; T cell; antitumor immunity
Authors: Georgios P Skandalakis; Daniel R Rivera; Caroline D Rizea; Alexandros Bouras; Joe Gerald Jesu Raj; Dominique Bozec; Constantinos G Hadjipanayis Journal: Int J Hyperthermia Date: 2020-07 Impact factor: 3.914