Journal for immunotherapy of cancer · 2025
In situ DC-primed vaccine combined with CD137 agonist elicits long-lasting antitumor immunity through cDC1-mediated tumor antigen-specific CD8+ T cell responses.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Wang Mengjiao, Qiu Li, Tang Cheng, Huang Danqing, Zheng Qiaocong, Li Zunyi, Zhang Zhenhui, Wei Shupei, Chen Lanfang, Huang Hongxin, Liu Jun, Zhou Junfeng, Lu Tao, Liu Guanxin, Nie Yingjie, Leng Qibin, Chen Tao
Аннотация
BACKGROUND: Intratumoral vaccines offer a promising avenue in cancer immunotherapy by harnessing the tumor microenvironment to stimulate immune responses. However, challenges persist in maximizing their effectiveness and addressing immune suppression within tumors.
METHODS: Conventional in situ vaccine (CisVac) and α-CD137 antibody were administered in implanted mouse models of lung and colon cancer to evaluate therapeutic efficacy. The initiation mechanism of CD8+ T cells was determined using antibody blockade and transgenic mouse models. Single-cell RNA sequencing was used to further characterize the activation mechanism of T cells.
RESULTS: Our findings indicate that this synergistic approach markedly inhibits tumor growth while eliciting a robust antitumor immune response, characterized by heightened activation and cytotoxic differentiation of CD8+ T cells, as well as the polarization of conventional dendritic cells (cDC1). Mechanistically, it promotes the cDC1-dependent proportion and cytokine production of tumor antigen-specific CD8+ T cells, mobilizes and establishes enduring systemic immune memory. Our single-cell transcriptome analyses revealed that the therapy facilitates a functional remodeling of regulatory T cells (Tregs) with upregulated inflammatory genes, potentially attenuating immune suppression. Cell-cell communication analyses highlighted interactions between CD4+ Th1-like/Th17 cells and monocytes/DCs through the CD40L-CD40 pathway, indicating potential intercellular regulatory mechanisms.
CONCLUSIONS: Our results highlight the transformative potential of the CisVac/α-CD137 combination in cancer immunotherapy, paving the way for further exploration of its clinical utility and long-term efficacy.
METHODS: Conventional in situ vaccine (CisVac) and α-CD137 antibody were administered in implanted mouse models of lung and colon cancer to evaluate therapeutic efficacy. The initiation mechanism of CD8+ T cells was determined using antibody blockade and transgenic mouse models. Single-cell RNA sequencing was used to further characterize the activation mechanism of T cells.
RESULTS: Our findings indicate that this synergistic approach markedly inhibits tumor growth while eliciting a robust antitumor immune response, characterized by heightened activation and cytotoxic differentiation of CD8+ T cells, as well as the polarization of conventional dendritic cells (cDC1). Mechanistically, it promotes the cDC1-dependent proportion and cytokine production of tumor antigen-specific CD8+ T cells, mobilizes and establishes enduring systemic immune memory. Our single-cell transcriptome analyses revealed that the therapy facilitates a functional remodeling of regulatory T cells (Tregs) with upregulated inflammatory genes, potentially attenuating immune suppression. Cell-cell communication analyses highlighted interactions between CD4+ Th1-like/Th17 cells and monocytes/DCs through the CD40L-CD40 pathway, indicating potential intercellular regulatory mechanisms.
CONCLUSIONS: Our results highlight the transformative potential of the CisVac/α-CD137 combination in cancer immunotherapy, paving the way for further exploration of its clinical utility and long-term efficacy.