In Vivo Reprogramming Strategies to Enhance Tumor Immunogenicity and T Cell Immunity

癌症免疫观点 ›› 2025, Vol. 1 ›› Issue (2) : 14-20.

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癌症免疫观点 ›› 2025, Vol. 1 ›› Issue (2) : 14-20. DOI: 10.70996/cip.00008

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In Vivo Reprogramming Strategies to Enhance Tumor Immunogenicity and T Cell Immunity

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Abstract

Cancer immunotherapies have achieved remarkable clinical success, yet their efficacy remains limited in tumors with low immunogenicity and insufficient antigen presentation within the tumor microenvironment. The absence or dysfunction of conventional type 1 dendritic cells (cDC1s)—the key antigen-presenting cells responsible for priming and sustaining cytotoxic T cell responses—represents a critical barrier to effective antitumor immunity. Recent advances in cellular reprogramming have opened new avenues to address this limitation through in vivo conversion of tumor cells themselves into immunogenic cell types. This review summarizes the current state of in vivo reprogramming strategies aimed at enhancing tumor immunogenicity and T cell-mediated immunity. We focus primarily on the pioneering approach of converting tumor cells into cDC1-like cells through adenoviral delivery of the transcription factors PU.1, IRF8, and BATF3 (PIB). This strategy induces profound remodeling of the tumor microenvironment, recruitment and expansion of polyclonal cytotoxic T cells, formation of tertiary lymphoid structures, and establishment of long-term systemic immunity in preclinical models. We discuss the mechanistic basis of this approach, compare it with alternative reprogramming strategies targeting other immune cell lineages, examine the challenges and limitations for clinical translation, and explore future directions for combination therapies. The ability to transform cancer cells from within into allies that orchestrate antitumor immune responses represents a paradigm shift in cancer immunotherapy with the potential to extend benefits to patients who currently fail to respond to existing treatments.

Key words

in vivo reprogramming / dendritic cells / tumor immunogenicity / T cell immunity / cancer immunotherapy / transcription factors / tumor microenvironment

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[J]. 癌症免疫观点. 2025, 1(2): 14-20 https://doi.org/10.70996/cip.00008
Zhi Wang.

In Vivo Reprogramming Strategies to Enhance Tumor Immunogenicity and T Cell Immunity

[J]. Cancer Immuno Perspectives. 2025, 1(2): 14-20 https://doi.org/10.70996/cip.00008

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