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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1508007
This article is part of the Research Topic Immune Tolerance Dual Role: Advancements in Cancer and Autoimmune Diseases View all 5 articles

Mixed radiation with different doses induces CCL17 to recruit CD8 + T cell to exert anti-tumor effects in non-small cell lung cancer

Provisionally accepted
Liuying Huang Liuying Huang 1Duo Wang Duo Wang 1Muchen Xu Muchen Xu 2Danqi Qian Danqi Qian 1Zhaohui Huang Zhaohui Huang 3Yulin Cao Yulin Cao 3Xiaohan Wu Xiaohan Wu 3Liang Ming Liang Ming 3Junhui Tang Junhui Tang 3Yuan Yin Yuan Yin 3*Leyuan Zhou Leyuan Zhou 1,2,4*
  • 1 Department of Radiation Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Liaoning Province, China
  • 2 Department of Radiation Oncology, The Fourth Affiliated Hospital of Soochow University, Suzhou, China
  • 3 Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, China
  • 4 State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, Liaoning Province, China

The final, formatted version of the article will be published soon.

    Background: Different doses of radiotherapy (RT) exert diverse effects on tumor immunity, although the precise irradiation method remains unknown. This study sought to elucidate the influence of combining different doses of RT with immune checkpoint inhibitors (ICIs) on the infiltration of CD8 + T cells within tumors, thereby augmenting the anti-tumor response.Methods: Constructing a mouse model featuring bilateral lung cancer tumors subjected to high and low dose irradiation, the analysis of RNA transcriptome sequencing data and immunohistochemical validation for tumors exposed to various dosages guided the selection of the optimal low-dose irradiation scheme. Subsequently, upon the integration of immune checkpoint inhibitors (ICIs) therapy, the infiltration of immune cells within the tumor was ascertained via immunohistochemistry (IHC) and flow cytometry (FCM). Finally, through bioinformatics analysis and experimental verification, potential strategies to bolster the anti-tumor immune response were investigated. Results: In comparison to the administration of 20Gy alone to the primary tumor, supplementing with 6Gy directed at the abscopal tumor produces a more pronounced abscopal response. The synergy of 20Gy, 6Gy, and ICIs markedly boosts the efficiency of ICIs. According to the findings from IHC and FCM studies, the triple therapy group exhibits a heightened infiltration of immune cells into the tumor, largely attributable to the augmented expression of CCL17 within the tumor under these irradiation regimens, which subsequently draws CD8+ T cells to infiltrate the tumor site, exerting cytotoxic effects.Our study shows that the combined application of 20Gy and 6Gy can enhance the infiltration of tumor CD8 + T cells in mice and improve the effectiveness of immunotherapy.

    Keywords: Lung cancer1, Radiothearpy2, Animal research3, immunotherapy4, combination therapy5

    Received: 08 Oct 2024; Accepted: 23 Dec 2024.

    Copyright: © 2024 Huang, Wang, Xu, Qian, Huang, Cao, Wu, Ming, Tang, Yin and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Yuan Yin, Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, China
    Leyuan Zhou, Department of Radiation Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Liaoning Province, China

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