Kalbasi, A. & Ribas, A. Tumour-intrinsic resistance to immune checkpoint blockade. Nat. Rev. Immunol. 20, 25–39 (2020).
Sharma, P., Hu-Lieskovan, S., Wargo, J. A. & Ribas, A. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell 168, 707–723 (2017).
Oliveira, G. & Wu, C. J. Dynamics and specificities of T cells in cancer immunotherapy. Nat. Rev. Cancer 23, 295–316 (2023).
Emens, L. A. et al. Cancer immunotherapy: opportunities and challenges in the rapidly evolving clinical landscape. Eur. J. Cancer 81, 116–129 (2017).
Chow, A., Perica, K., Klebanoff, C. A. & Wolchok, J. D. Clinical implications of T cell exhaustion for cancer immunotherapy. Nat. Rev. Clin. Oncol. 19, 775–790 (2022).
Larson, R. C. & Maus, M. V. Recent advances and discoveries in the mechanisms and functions of CAR T cells. Nat. Rev. Cancer 21, 145–161 (2021).
Lin, M. J. et al. Cancer vaccines: the next immunotherapy frontier. Nat. Cancer 3, 911–926 (2022).
Kirchhammer, N., Trefny, M. P., Maur, P. A. D., Läubli, H. & Zippelius, A. Combination cancer immunotherapies: emerging treatment strategies adapted to the tumor microenvironment. Sci. Transl. Med. 14, eabo3605 (2022).
Miller, C. L. et al. Systemic delivery of a targeted synthetic immunostimulant transforms the immune landscape for effective tumor regression. Cell Chem. Biol. 29, 451–462 (2022).
Marabelle, A., Tselikas, L., de Baere, T. & Houot, R. Intratumoral immunotherapy: using the tumor as the remedy. Ann. Oncol. 28, 33–43 (2017).
Melero, I., Castanon, E., Alvarez, M., Champiat, S. & Marabelle, A. Intratumoural administration and tumour tissue targeting of cancer immunotherapies. Nat. Rev. Clin. Oncol. 18, 558–576 (2021).
Dieu-Nosjean, M. C. et al. Long-term survival for patients with non-small-cell lung cancer with intratumoral lymphoid structures. J. Clin. Oncol. 26, 4410–4417 (2008).
Lee, Y. et al. Recruitment and activation of naive T cells in the islets by lymphotoxin β receptor-dependent tertiary lymphoid structure. Immunity 25, 499–509 (2006).
Peske, J. D. et al. Effector lymphocyte-induced lymph node-like vasculature enables naive T-cell entry into tumours and enhanced anti-tumour immunity. Nat. Commun. 6, 7114 (2015).
Heras-Murillo, I., Adán-Barrientos, I., Galán, M., Wculek, S. K. & Sancho, D. Dendritic cells as orchestrators of anticancer immunity and immunotherapy. Nat. Rev. Clin. Oncol. 21, 257–277 (2024).
Saxena, M., van der Burg, S. H., Melief, C. J. M. & Bhardwaj, N. Therapeutic cancer vaccines. Nat. Rev. Cancer 21, 360–378 (2021).
Lin, J. H. et al. Type 1 conventional dendritic cells are systemically dysregulated early in pancreatic carcinogenesis. J. Exp. Med. 217, e20190673 (2020).
Meier, S. L., Satpathy, A. T. & Wells, D. K. Bystander T cells in cancer immunology and therapy. Nat. Cancer 3, 143–155 (2022).
Simoni, Y. et al. Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates. Nature 557, 575–579 (2018).
Kalaora, S. et al. Identification of bacteria-derived HLA-bound peptides in melanoma. Nature 592, 138–143 (2021).
Rosato, P. C. et al. Virus-specific memory T cells populate tumors and can be repurposed for tumor immunotherapy. Nat. Commun. 10, 567 (2019).
Jhunjhunwala, S., Hammer, C. & Delamarre, L. Antigen presentation in cancer: insights into tumour immunogenicity and immune evasion. Nat. Rev. Cancer 21, 298–312 (2021).
Zimmermannova, O. et al. Restoring tumor immunogenicity with dendritic cell reprogramming. Sci. Immunol. 8, eadd4817 (2023).
Ascic, E. et al. In vivo dendritic cell reprogramming for cancer immunotherapy. Science 386, eadn9083 (2024).
Zhu, Y. et al. Bioorthogonal cleavage chemistry: harnessing the bond-break reactions for biomolecule manipulations in living systems. Chin. J. Chem. 43, 553–566 (2025).
Dong, J. J., Krasnova, L., Finn, M. G. & Sharpless, K. B. Sulfur(VI) fluoride exchange (SuFEx): another good reaction for click chemistry. Angew. Chem. Int. Edn 53, 9430–9448 (2014).
Wang, N. X. et al. Genetically encoding fluorosulfate-L-tyrosine to react with lysine, histidine, and tyrosine via SuFEx in proteins. J. Am. Chem. Soc. 140, 4995–4999 (2018).
Yu, B. et al. Accelerating PERx reaction enables covalent nanobodies for potent neutralization of SARS-CoV-2 and variants. Chem 8, 2766–2783 (2022).
Wang, L. & Schultz, P. G. Expanding the genetic code. Angew. Chem. Int. Edn 44, 34–66 (2005).
Chin, J. W. Expanding and reprogramming the genetic code. Nature 550, 53–60 (2017).
Cheng, Z. J. J. et al. Novel PD-1 blockade bioassay to assess therapeutic antibodies in PD-1 and PD-L1 immunotherapy programs. Cancer Res. 75, 5440 (2015).
Joffre, O. P., Segura, E., Savina, A. & Amigorena, S. Cross-presentation by dendritic cells. Nat. Rev. Immunol. 12, 557–569 (2012).
Rodríguez-Silvestre, P. et al. Perforin-2 is a pore-forming effector of endocytic escape in cross-presenting dendritic cells. Science 380, 1258–1265 (2023).
Kroemer, G., Galassi, C., Zitvogel, L. & Galluzzi, L. Immunogenic cell stress and death. Nat. Immunol. 23, 487–500 (2022).
Jin, M. Z. & Wang, X. P. Immunogenic cell death-based cancer vaccines. Front. Immunol. 12, 697964 (2021).
Oba, T. et al. Overcoming primary and acquired resistance to anti-PD-L1 therapy by induction and activation of tumor-residing cDC1s. Nat. Commun. 11, 5415 (2020).
Vescovini, R. et al. Massive load of functional effector CD4+ and CD8+ T cells against cytomegalovirus in very old subjects. J. Immunol. 179, 4283–4291 (2007).
Lin, F. et al. Multimodal targeting chimeras enable integrated immunotherapy leveraging tumor-immune microenvironment. Cell 187, 7470–7491 (2024).
Shalhout, S. Z., Miller, D. M., Emerick, K. S. & Kaufman, H. L. Therapy with oncolytic viruses: progress and challenges. Nat. Rev. Clin. Oncol. 20, 160–177 (2023).
Harrington, K., Freeman, D. J., Kelly, B., Harper, J. & Soria, J. C. Optimizing oncolytic virotherapy in cancer treatment. Nat. Rev. Drug Discov. 18, 689–706 (2019).
Wang, G. et al. An engineered oncolytic virus expressing PD-L1 inhibitors activates tumor neoantigen-specific T cell responses. Nat. Commun. 11, 1395 (2020).
Chen, Y. X. et al. An oncolytic virus–T cell chimera for cancer immunotherapy. Nat. Biotechnol. 42, 1876–1887 (2024).
Chen, X. Y. et al. An oncolytic virus delivering tumor-irrelevant bystander T cell epitopes induces anti-tumor immunity and potentiates cancer immunotherapy. Nat. Cancer 5, 1063–1081 (2024).
Cruz, F. M., Chan, A. M. D. & Rock, K. L. Pathways of MHC I cross-presentation of exogenous antigens. Semin. Immunol. 66, 101729 (2023).
Banik, S. M. et al. Lysosome-targeting chimaeras for degradation of extracellular proteins. Nature 584, 291–297 (2020).
Ahn, G. et al. LYTACs that engage the asialoglycoprotein receptor for targeted protein degradation. Nat. Chem. Biol. 17, 937–946 (2021).
Zhou, Y. X., Teng, P., Montgomery, N. T., Li, X. L. & Tang, W. P. Development of triantennary N-acetylgalactosamine conjugates as degraders for extracellular proteins. ACS Cent. Sci. 7, 499–506 (2021).
Cotton, A. D., Nguyen, D. P., Gramespacher, J. A., Seiple, I. B. & Wells, J. A. Development of antibody-based PROTACs for the degradation of the cell-surface immune checkpoint protein PD-L1. J. Am. Chem. Soc. 143, 593–598 (2021).
Zhang, H. et al. Covalently engineered nanobody chimeras for targeted membrane protein degradation. J. Am. Chem. Soc. 143, 16377–16382 (2021).
Sefrin, J. P. et al. Sensitization of tumors for attack by virus-specific CD8+ T-cells through antibody-mediated delivery of immunogenic T-cell epitopes. Front. Immunol. 10, 1962 (2019).
Millar, D. G. et al. Antibody-mediated delivery of viral epitopes to tumors harnesses CMV-specific T cells for cancer therapy. Nat. Biotechnol. 38, 420–425 (2020).
van der Wulp, W. et al. Comparison of methods generating antibody-epitope conjugates for targeting cancer with virus-specific T cells. Front. Immunol. 14, 1183914 (2023).
Zimmermannova, O., Caiado, I., Ferreira, A. G. & Pereira, C. F. Cell fate reprogramming in the era of cancer immunotherapy. Front. Immunol. 12, 714822 (2021).
Rapino, F. et al. C/EBPα induces highly efficient macrophage transdifferentiation of B lymphoma and leukemia cell lines and impairs their tumorigenicity. Cell Rep. 3, 1153–1163 (2013).
McClellan, J. S., Dove, C., Gentles, A. J., Ryan, C. E. & Majeti, R. Reprogramming of primary human Philadelphia chromosome-positive B cell acute lymphoblastic leukemia cells into nonleukemic macrophages. Proc. Natl Acad. Sci. USA 112, 4074–4079 (2015).
Linde, M. H. et al. Reprogramming cancer into antigen-presenting cells as a novel immunotherapy. Cancer Discov. 13, 1164–1185 (2023).
Wang, J. L., Sun, S. C. & Deng, H. K. Chemical reprogramming for cell fate manipulation methods, applications, and perspectives. Cell Stem Cell 30, 1130–1147 (2023).
Guan, J. Y. et al. Chemical reprogramming of human somatic cells to pluripotent stem cells. Nature 605, 325–331 (2022).
Hu, Y. Y. et al. Induction of mouse totipotent stem cells by a defined chemical cocktail. Nature 617, 792–797 (2023).
Manjunath, N. et al. Effector differentiation is not prerequisite for generation of memory cytotoxic T lymphocytes. J. Clin. Invest. 108, 871–878 (2001).
Ge, Y. et al. Enzyme-mediated intercellular proximity labeling for detecting cell-cell interactions. J. Am. Chem. Soc. 141, 1833–1837 (2019).
Yin, S. et al. Patient-derived tumor-like cell clusters for drug testing in cancer therapy. Sci. Transl. Med. 12, eaaz1723 (2020).
Dijkstra, K. K. et al. Generation of tumor-reactive T cells by co-culture of peripheral blood lymphocytes and tumor organoids. Cell 174, 1586–1598 (2018).
Cattaneo, C. M. et al. Tumor organoid-T-cell coculture systems. Nat. Protoc. 15, 15–39 (2020).
Yin, S. et al. Patient-derived tumor-like cell clusters for personalized chemo- and immunotherapies in non-small cell lung cancer. Cell Stem Cell 31, 717–733 (2024).
