Bioactive Nanomaterials for Cancer Immunotherapy

Zhan-Zhan Zhang; Kai-Jia Liu; Qiu-Shi Li; Yang Liu

doi:10.1007/s10118-026-3567-z

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Bioactive Nanomaterials for Cancer Immunotherapy

Special Topic: Distinguished Young Scholars in Polymer Science | Updated：2026-07-01

- Bioactive Nanomaterials for Cancer Immunotherapy
- Chinese Journal of Polymer Science Vol. 44, Issue 7, Pages: 1984-2001(2026)
- Affiliations：
  
  State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Functional Polymer Materials Ministry of Education, College of Chemistry, Nankai University, Tianjin 300071, China
- Author bio：
  
  Yliu@nankai.edu.cn
- Funds：
- DOI：10.1007/s10118-026-3567-z
  CLC：
- Received：30 December 2025，
  
  Accepted：10 January 2026，
  
  Online First：24 April 2026，
  
  Published：05 July 2026
- Accepted：
Scan QR Code
Zhang, Z. Z.; Liu, K. J.; Li, Q. S.; Liu, Y. Bioactive nanomaterials for cancer immunotherapy. Chinese J. Polym. Sci. 2026, 44, 1984–2001

Zhan-Zhan Zhang, Kai-Jia Liu, Qiu-Shi Li, et al. Bioactive Nanomaterials for Cancer Immunotherapy[J]. Chinese Journal of Polymer Science, 2026, 44(7): 1984-2001.
Zhang, Z. Z.; Liu, K. J.; Li, Q. S.; Liu, Y. Bioactive nanomaterials for cancer immunotherapy. Chinese J. Polym. Sci. 2026, 44, 1984–2001 DOI： 10.1007/s10118-026-3567-z.

Zhan-Zhan Zhang, Kai-Jia Liu, Qiu-Shi Li, et al. Bioactive Nanomaterials for Cancer Immunotherapy[J]. Chinese Journal of Polymer Science, 2026, 44(7): 1984-2001. DOI： 10.1007/s10118-026-3567-z.

摘要

This review systemically summarizes their studies on bioactive nanomaterials for cancer immunotherapy and highlights three complementary strategies: surface-adaptive nanomaterials to overcome physiological barriers

antigen-engineering nanoplatforms that enhance tumor immunogenicity

and nanomaterials that modulate tumor microenvironment to relieve immune suppression

collectively reinvigorating robust antitumor immune responses.

Abstract

Cancer immunotherapy has revolutionized oncology by harnessing the immune system to recognize and eliminate malignant cells

yet its clinical efficacy is often limited by tumor immune evasion

low immunogenicity

and an immunosuppressive tumor microenvironment (TME). Recent advances in nanotechnology offer opportunities to overcome these barriers by precisely modulating both tumor and immune landscapes. In this review

we summarize three representative strategies developed by our group: (i) surface-adaptive nanomaterials (SANs)

which respond dynamically to physiological and tumor-specific cues to enable prolonged systemic circulation

efficient barrier translocation

and controlled intratumoral activation; (ii) antigen-engineering nanoplatforms

designed to enhance tumor immunogenicity

via

delivering exogenous antigens to antigen-presenting cells (APCs)

inducing tumor cells to re-express or re-generate

or anchoring immunogenic epitopes onto tumor surfaces

thereby promoting T cell activation and converting “cold” tumors into “hot” ones; and (iii) TME-modulating nanomaterials

which alleviate immune suppression

via

targeted delivery of inhibitors

neutralization or degra

dation of suppressive cytokines

and gene-level reprogramming of tumors to restore effector immunity. Together

these approaches provide a multifaceted framework for reinvigorating antitumor immune responses and offer mechanistic insights and design principles for the next generation of bioactive polymeric nanomaterials with potential translational application in cancer immunotherapy.

关键词

Keywords

references

Bosland, M. C. Global health and cancer. Lancet 2019 , 393 , 983..

Chen, S. M.; Cao, Z.; Prettner, K.; Kuhn, M.; Yang, J. T.; Jiao, L. R.; Wang, Z. R.; Li, W. M.; Geldsetzer, P.; Baernighausen, T.; Bloom, D. E.; Wang, C. Estimates and projections of the global economic cost of 29 cancers in 204 countries and territories from 2020 to 2050. JAMA Oncol. 2023 , 9 , 465−472..

Bray, F.; Laversanne, M.; Sung, H.; Ferlay, J.; Siegel, R. L.; Soerjomataram, I.; Jemal, A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Ca-Cancer J. Clin. 2024 , 74 , 229−263..

Guan, X. M. Cancer metastases: challenges and opportunities. Acta Pharm. Sin. B 2015 , 5 , 402−418..

Yang, Y. Cancer immunotherapy: harnessing the immune system to battle cancer. J Clin. Invest. 2015 , 125 , 3335−3337..

[Emens, L. A.; Romero, P. J.; Anderson, A. C.; Bruno, T. C.; Capitin i, C. M.; Collyar, D.; Gulley, J. L.; Hwu, P.; Posey, A. D., Jr.; Silk, A. W.; Wargo, J. A. Challenges and opportunities in cancer immunotherapy: a Society for Immunotherapy of Cancer (SITC) strategic vision. J. Immunother. Cancer 2024, 12 , e009063..

[Liu, D.; Tian, J.; Yu, L.; Luo, H.; Rong, H.; Tong, Y.; Gao, X.; Yin, J. A modular metalloprotein in situ vaccine for cancer immunotherapy in mouse models of breast cancer. Sci. Transl. Med. 2025 , 17 , eadr1777..

Sharma, P.; Goswami, S.; Raychaudhuri, D.; Siddiqui, B. A.; Singh, P.; Nagarajan, A.; Liu, J.; Subudhi, S. K.; Poon, C.; Gant, K. L.; Herbrich, S. M.; Anandhan, S.; Islam, S.; Amit, M.; Anandappa, G.; Allison, J. P. Immune checkpoint therapy—current perspectives and future directions. CELL 2023 , 186 , 1652−1669..

Freeman, G. J.; Long, A. J.; Iwai, Y.; Bourque, K.; Chernova, T.; Nishimura, H.; Fitz, L. J.; Malenkovich, N.; Okazaki, T.; Byrne, M. C.; Horton, H. F.; Fouser, L.; Carter, L.; Ling, V.; Bowman, M. R.; Carreno, B. M.; Collins, M.; Wood, C. R.; Honjo, T. Engagement of the Pd-1 Immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J. Exp. Med. 2000 , 192 , 1027−1034..

[Seiwert, T. Y.; Weiss, J.; Baxi, S. S.; Ahn, M.-J.; Fayette, J.; Gillison, M. L.; Machiels, J.-P. H.; Takahashi, S.; Melillo, G.; Franks, A.; Emeribe, U.; Raben, D.; McDevitt, M.; Psyrri, A. A phase 3, randomized, open-label study of first-line durvalumab (MEDI4736) ± tremelimumab versus standard of care (SoC; EXTREME regimen) in recurrent/metastatic (R/M) SCCHN: KESTREL. J. Clin. Oncol. 2016 , 34 , TPS6101..

Larkin, J.; Chiarion-Sileni, V.; Gonzalez, R.; Grob, J. J.; Cowey, C. L.; Lao, C. D.; Schadendorf, D.; Dummer, R.; Smylie, M.; Rutkowski, P.; Ferrucci, P. F.; Hill, A.; Wagstaff, J.; Carlino, M. S.; Haanen, J. B.; Maio, M.; Marquez-Rodas, I.; McArthur, G. A.; Ascierto, P. A.; Long, G. V.; Callahan, M. K.; Postow, M. A.; Grossmann, K.; Sznol, M.; Dreno, B.; Bastholt, L.; Yang, A.; Rollin, L. M.; Horak, C.; Hodi, F. S.; Wolchok, J. D. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N. Engl. J. Med. 2015 , 373 , 23−34..

Wolchok, J. D.; Kluger, H.; Callahan, M. K.; Postow, M. A.; Rizvi, N. A.; Lesokhin, A. M.; Segal, N. H.; Ariyan, C. E.; Gordon, R. A.; Reed, K.; Burke, M. M.; Caldwell, A.; Kronenberg, S. A.; Agunwamba, B. U.; Zhang, X. L.; Lowy, I.; Inzunza, H. D.; Feely, W.; Horak, C. E.; Hong, Q.; Korman, A. J.; Wigginton, J. M.; Gupta, A.; Sznol, M. Nivolumab plus ipilimumab in advanced melanoma. N. Engl. J. Med. 2013 , 369 , 122−133..

[Cesano, A.; Augustin, R.; Barrea, L.; Bedognetti, D.; Bruno, T. C.; Carturan, A.; Hammer, C.; Ho, W. S.; Kather, J. N.; Kirchhoff, T.; Lu, R. O.; McQuade, J.; Najjar, Y. G.; Pietrobon, V.; Ruella, M.; Shen, R.; Soldati, L.; Spencer, C.; Betof Warner, A.; Warren, S.; Ziv, E.; Marincola, F. M. Advances in the understanding and therapeutic manipulation of cancer immune responsiveness: a Society for Immunotherapy of Cancer (SITC) review. J. Immunother. Cancer 2025, 13 , e008876..

Haitz, K.; Khosravi, H.; Lin, J. Y.; Menge, T.; Nambudiri, V. E. Review of talimogene laherparepvec: a first-in-class oncolytic viral treatment of advanced melanoma. J. Am. Acad. Dermatol. 2020 , 83 , 189−196..

Vanneman, M.; Dranoff, G. Combining immunotherapy and targeted therapies in cancer treatment. Nat. Rev. Cancer 2012 , 12 , 237−251..

Qin, H.; Zhou, Z.; Shi, R.; Mai, Y.; Xu, Y.; Peng, F.; Cheng, G.; Zhang, P.; Chen, W.; Chen, Y.; Chen, Y.; Xu, R.; Lu, Q. Insights into next-generation immunotherapy designs and tools: molecular mechanisms and therapeutic prospects. J. Hematol. Oncol. 2025 , 18 , 62..

Hu, B.; Yu, M.; Ma, X.; Sun, J.; Liu, C.; Wang, C.; Wu, S.; Fu, P.; Yang, Z.; He, Y.; Zhu, Y.; Huang, C.; Yang, X.; Shi, Y.; Qiu, S.; Sun, H.; Zhu, A. X.; Zhou, J.; Xu, Y.; Zhu, D.; Fan, J. IFNα Potentiates Anti-PD-1 efficacy by remodeling glucose metabolism in the hepatocellular carcinoma microenvironment. Cancer Discovery 2022 , 12 , 1718−1741..

Yang, L.; Li, A.; Lei, Q.; Zhang, Y. Tumor-intrinsic signaling pathways: key roles in the regulation of the immunosuppressive tumor microenvironment. J. Hematol. Oncol. 2019 , 12 , 125..

Ramos-Casals, M.; Brahmer, J. R.; Callahan, M. K.; Flores-Chávez, A.; Keegan, N.; Khamashta, M. A.; Lambotte, O.; Mariette, X.; Prat, A.; Suárez-Almazor, M. E. Immune-related adverse events of checkpoint inhibitors. Nat. Rev. Dis. Prim. 2020 , 6 , 38..

Cleveland, A. H.; Fan, Y. Reprogramming endothelial cells to empower cancer immunotherapy. Trends Mol. Med. 2024 , 30 , 126−135..

[Ferrara, B.; Pignatelli, C.; Cossutta, M.; Citro, A.; Courty, J.; Piemonti, L. The extracellular matrix in pancreatic cancer: description of a complex network and promising therapeutic options Cancers 2021 , 13 , 4442..

Linderman, S. W.; DeRidder, L.; Sanjurjo, L.; Foote, M. B.; Alonso, M. J.; Kirtane, A. R.; Langer, R.; Traverso, G. Enhancing immunotherapy with tumour-responsive nanomaterials. Nat. Rev. Clin. Oncol. 2025 , 22 , 262−282..

Au, J. L. S.; Yeung, B. Z.; Wientjes, M. G.; Lu, Z.; Wientjes, M. G. Delivery of cancer therapeutics to extracellular and intracellular targets: Determinants, barriers, challenges and opportunities. Adv. Drug Delivery Rev. 2016 , 97 , 280−301..

Liu, J. F.; Lan, Z.; Ferrari, C.; Stein, J. M.; Higbee-Dempsey, E.; Yan, L.; Amirshaghaghi, A.; Cheng, Z.; Issadore, D.; Tsourkas, A. Use of oppositely polarized external magnets to improve the accumulation and penetration of magnetic nanocarriers into solid tumors. ACS Nano 2020 , 14 , 142−152..

Dersh, D.; Phelan, J. D.; Gumina, M. E.; Wang, B.; Arbuckle, J. H.; Holly, J.; Kishton, R. J.; Markowitz, T. E.; Seedhom, M. O.; Fridlyand, N.; Wright, G. W.; Huang, D. W.; Ceribelli, M.; Thomas, C. J.; Lack, J. B.; Restifo, N. P.; Kristie, T. M.; Staudt, L. M.; Yewdell, J. W. Genome-wide screens identify lineage- and tumor-specific genes modulating mhc-i- and mhc-ii-restricted immunosurveillance of human lymphomas. Immunity 2021 , 54 , 116−131..

Zapata, L.; Caravagna, G.; Williams, M. J.; Lakatos, E.; AbdulJabbar, K.; Werner, B.; Chowell, D.; James, C.; Gourmet, L.; Milite, S.; Acar, A.; Riaz, N.; Chan, T. A.; Graham, T. A.; Sottoriva, A. Immune selection determines tumor antigenicity and influences response to checkpoint inhibitors. Nat. Genet. 2023 , 55 , 451−460..

Pitt, J. M.; Marabelle, A.; Eggermont, A.; Soria, J. C.; Kroemer, G.; Zitvogel, L. Targeting the tumor microenvironment: removing obstruction to anticancer immune responses and immunotherapy. Ann. Oncol. 2016 , 27 , 1482−1492..

[Gu, J.; Li, Y.; Chen, Q.; Song, Z.; Qian, Q.; Liang, Y.; Huang, T.; Qiao, L.; Li, X.; Yu, M.; Liu, M.; Zhou, J.; Shao, Q.; Xu, X.; Zeiser, R.; Lu, L. Tumor-produced ammonia is metabolized by regulatory T cells to further impede anti-tumor immunity. CELL 2025 , 189 , 418−434..

Alicea Pauneto, C. d. M.; Riesenberg, B. P.; Gandy, E. J.; Kennedy, A. S.; Clutton, G. T.; Hem, J. W.; Hurst, K. E.; Hunt, E. G.; Green, J. M.; Miller, B. C.; Angus, S. P.; Johnson, G. L.; Esther, R. J.; Guerriero, J. L.; Gao, P.; Soto-Pantoja, D. R.; Ferris, R. L.; Modliszewski, J. L.; Coleman, M. F.; Chung, H. K.; Milner, J. J.; Moschos, S. J.; Wiseman, R. L.; Thaxton, J. E. Intra-tumoral hypoxia promotes CD8 < sup > + < /sup > T cell dysfunction via chronic activation of integrated stress response transcription factor ATF4. Immunity 2025 , 58 , 2489−2504..

Tang, T.; Huang, X.; Zhang, G.; Hong, Z.; Bai, X.; Liang, T. Advantages of targeting the tumor immune microenvironment over blocking immune checkpoint in cancer immunotherapy. Signal Transduction Targeted Ther. 2021 , 6 , 72..

Bertrand, N.; Wu, J.; Xu, X. Y.; Kamaly, N.; Farokhzad, O. C. Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. Adv. Drug Delivery Rev. 2014 , 66 , 2−25..

Ferrari, M. Cancer nanotechnology: opportunities and challenges. Nat. Rev. Cancer 2005 , 5 , 161−171..

Li, J.; Gao, X.; Wang, Y.; Xia, T.; Zhao, Y.; Meng, H. Precision design of engineered nanomaterials to guide immune systems for disease treatment. Matter 2022 , 5 , 1162−1191..

Nel, A. E.; Mädler, L.; Velegol, D.; Xia, T.; Hoek, E. M. V.; Somasundaran, P.; Klaessig, F.; Castranova, V.; Thompson, M. Understanding biophysicochemical interactions at the nano-bio interface. Nat. Mater. 2009 , 8 , 543−557..

Austria, E.; Bilek, M.; Varamini, P.; Akhavan, B. Breaking biological barriers: engineering polymeric nanoparticles for cancer therapy. Nano Today 2025 , 60 , 102552..

Ren, Y.; Fan, Q.; Yao, X.; Zhang, J.; Wen, K.; Qu, X.; Sun, B.; Wu, H.; Dong, Z. A phosphatidylserine-targeted self-amplifying nanosystem improves tumor accumulation and enables efficient tumor therapy by modulating anticancer immunity. Biomaterials 2026 , 324 , 123526..

Wu, Y.; Li, Y.; Hu, Z.; Li, Y.; Zhang, S.; Bao, X.; Zhou, Y.; Gao, Y.; Li, Y.; Zhang, Z. Extracellular matrix-trapped bioinspired lipoprotein prolongs tumor retention to potentiate antitumor immunity. Adv. Mater. 2024 , 36 , 2310982..

Doedens, A. L.; Rubinstein, M. P.; Gross, E. T.; Best, J. A.; Craig, D. H.; Baker, M. K.; Cole, D. J.; Bui, J. D.; Goldrath, A. W. Molecular programming of tumor-infiltrating CD8+ T cells and IL15 resistance. Cancer Immunol. Res. 2016 , 4 , 799−811..

Zhong, X.; He, X.; Wang, Y.; Hu, Z.; Huang, H.; Zhao, S.; Wei, P.; Li, D. Warburg effect in colorectal cancer: the emerging roles in tumor microenvironment and therapeutic implications. J. Hematol. Oncol. 2022 , 15 , 160..

Schwartz, L.; Seyfried, T.; Alfarouk, K. O.; Da Veiga Moreira, J.; Fais, S. Out of Warburg effect: an effective cancer treatment targeting the tumor specific metabolism and dysregulated pH. Semin. Cancer Biol. 2017 , 43 , 134−138..

Liu, Y.; Dai, R.; Wei, Q.; Li, W.; Zhu, G.; Chi, H.; Guo, Z.; Wang, L.; Cui, C.; Xu, J.; Ma, K. Dual-functionalized janus mesoporous silica nanoparticles with active targeting and charge reversal for synergistic tumor-targeting therapy. ACS Appl. Mater. Interfaces 2019 , 11 , 44582−44592..

Zhou, Q.; Hou, Y.; Zhang, L.; Wang, J.; Qiao, Y.; Guo, S.; Fan, L.; Yang, T.; Zhu, L.; Wu, H. Dual-pH sensitive charge-reversal nanocomplex for tumor-targeted drug delivery with enhanced anticancer activity. Theranostics 2017 , 7 , 1806−1819..

Ling, B.; Yang, L.; Wang, C.; Dong, L.; Yang, Y.; Wang, L.; Zha ng, J.; Yuan, Y. Cascade-responsive upconversion nanoplatform for efficient cell nucleus targeting and boosted photodynamic tumor therapy. ACS Mater. Lett. 2024 , 6 , 5256−5265..

Liu, Q.; Zhao, K.; Wang, C.; Zhang, Z.; Zheng, C.; Zhao, Y.; Zheng, Y.; Liu, C.; An, Y.; Shi, L.; Kang, C.; Liu, Y. Multistage delivery nanoparticle facilitates efficient CRISPR/dCas9 activation and tumor growth suppression in Vivo. Adv. Sci. (Weinh) 2019 , 6 , 1801423..

Kojima, C.; Yao, J.; Nakajima, K.; Suzuki, M.; Tsujimoto, A.; Kuge, Y.; Ogawa, M.; Matsumoto, A. Attenuated polyethylene glycol immunogenicity and overcoming accelerated blood clearance of a fully PEGylated dendrimer. Int. J. Pharm. 2024 , 659 , 124193..

Heck, A. G.; Stickdorn, J.; Rosenberger, L. J.; Scherger, M.; Woller, J.; Eigen, K.; Bros, M.; Grabbe, S.; Nuhn, L. Polymerizable 2-propionic-3-methylmaleic anhydrides as a macromolecular carrier platform for ph-responsive immunodrug delivery. J. Am. Chem. Soc. 2023 , 145 , 27424−27436..

Liu, Q.; Cai, J.; Zheng, Y.; Tan, Y.; Wang, Y.; Zhang, Z.; Zheng, C.; Zhao, Y.; Liu, C.; An, Y.; Jiang, C.; Shi, L.; Kang, C.; Liu, Y. NanoRNP overcomes tumor heterogeneity in cancer treatment. Nano Lett. 2019 , 19 , 7662−7672..

Gao, G. H.; Park, M. J.; Li, Y.; Im, G. H.; Kim, J. H.; Kim, H. N.; Lee, J. W.; Jeon, P.; Bang, O. Y.; Lee, J. H.; Lee, D. S. The use of pH-sensitive positively charged polymeric micelles for protein delivery. Biomaterials 2012 , 33 , 9157−9164..

Ou, H.; Cheng, T.; Zhang, Y.; Liu, J.; Ding, Y.; Zhen, J.; Shen, W.; Xu, Y.; Yang, W.; Niu, P.; Liu, J.; An, Y.; Liu, Y.; Shi, L. Surface-adaptive zwitterionic nanoparticles for prolonged bloodcirculation time and enhanced cellular uptake in tumor cells. Acta Biomater. 2018 , 65 , 339−348..

Cheng, T.; Zhang, Y.; Liu, J.; Ding, Y.; Ou, H.; Huang, F.; An, Y.; Liu, Y.; Liu, J.; Shi, L. Ligand-switchable micellar nanocarriers for prolonging circulation time and enhancing targeting efficiency. ACS Appl. Mater. Interfaces 2018 , 10 , 5296−5304..

[Rey-Keim, S.; Schito, L. Origins and molecular effects of hypoxia in cancer. Semin. Cancer Biol . 2024, 106-107 , 166-178..

Liao, C.; Liu, X.; Zhang, C.; Zhang, Q. Tumor hypoxia: From basic knowledge to therapeutic implications. Semin. Cancer Biol. 2023 , 88 , 172−186..

Meng, X.; Klaasen, H.; Viergutz, L.; Schulze Lammers, B.; Witteler, M. C.; Mönig, H.; Amirjalayer, S.; Liu, L.; Neugebauer, J.; Gao, H.-Y.; Studer, A.; Fuchs, H. Azo bond formation on metal surfaces. Angew. Chem., Int. Ed. 2021 , 60 , 1458−1464..

Zhang, Z.; Yue, Y.-X.; Xu, L.; Wang, Y.; Geng, W.-C.; Li, J.-J.; Kong, X.-l.; Zhao, X.; Zheng, Y.; Zhao, Y.; Shi, L.; Guo, D.-S.; Liu, Y. Macrocyclic-amphiphile-based self-assembled nanoparticles for ratiometric delivery of therapeutic combinations to tumors. Adv. Mater. 2021 , 33 , 2007719..

Huang, J.; Yang, B.; Peng, Y.; Huang, J.; Wong, S. H. D.; Bian, L.; Zhu, K.; Shuai, X.; Han, S. Nanomedicine-boosting tumor immunogenicity for enhanced immunotherapy. Adv. Funct. Mater. 2021 , 31 , 2011171..

Munn, D. H.; Mellor, A. L. Indoleamine 2,3-dioxygenase and tumor-induced tolerance. J. Clin. Invest. 2007 , 117 , 1147−1154..

Jhunjhunwala, S.; Hammer, C.; Delamarre, L. Antigen presentation in cancer: insights into tumour immunogenicity and immune evasion. Nat. Rev. Cancer 2021 , 21 , 298−312..

Huntington, N. D.; Cursons, J.; Rautela, J. The cancer–natural killer cell immunity cycle. Nat. Rev. Cancer 2020 , 20 , 437−454..

Ritter, A. T.; Shtengel, G.; Xu, C. S.; Weigel, A.; Hoffman, D. P.; Freeman, M.; Iyer, N.; Alivodej, N.; Ackerman, D.; Voskoboinik, I.; Trapani, J.; Hess, H. F.; Mellman, I. ESCRT-mediated membrane repair protects tumor-derived cells against T cell attack. Sci. 2022 , 376 , 377−382..

Sivori, S.; Vacca, P.; Del Zotto, G.; Munari, E.; Mingari, M. C.; Moretta, L. Human NK cells: surface receptors, inhibitory checkpoints, and translational applications. Cell. Mol. Immunol. 2019 , 16 , 430−441..

Zheng, C.; Wang, Q.; Wang, Y.; Zhao, X.; Gao, K.; Liu, Q.; Zhao, Y.; Zhang, Z.; Zheng, Y.; Cao, J.; Chen, H.; Shi, L.; Kang, C.; Liu, Y.; Lu, Y. In situ modification of the tumor cell surface with immunomodulating nanoparticles for effective suppression of tumor growth in mice. Adv. Mater. 2019 , 31 , 1902542..

Tumeh, P. C.; Harview, C. L.; Yearley, J. H.; Shintaku, I. P.; Taylor, E. J. M.; Robert, L.; Chmielowski, B.; Spasic, M.; Henry, G.; Ciobanu, V.; West, A. N.; Carmona, M.; Kivork, C.; Seja, E.; Cherry, G.; Gutierrez, A. J.; Grogan, T. R.; Mateus, C.; Tomasic, G.; Glaspy, J. A.; Emerson, R. O.; Robins, H.; Pierce, R. H.; Elashoff, D. A.; Robert, C.; Ribas, A. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 2014 , 515 , 568−571..

Willingham, S. B.; Volkmer, J. P.; Gentles, A. J.; Sahoo, D.; Dalerba, P.; Mitra, S. S.; Wang, J.; Contreras-Trujillo, H.; Martin, R.; Cohen, J. D.; Lovelace, P.; Scheeren, F. A.; Chao, M. P.; Weiskopf, K.; Tang, C.; Volkmer, A. K.; Naik, T. J.; Storm, T. A.; Mosley, A. R.; Edris, B.; Schmid, S. M.; Sun, C. K.; Chua, M. S.; Murillo, O.; Rajendran, P.; Cha, A. C.; Chin, R. K.; Kim, D.; Adorno, M.; Raveh, T.; Tseng, D.; Jaiswal, S.; Enger, P. O.; Steinberg, G. K.; Li, G.; So, S. K.; Majeti, R.; Harsh, G. R.; van de Rijn, M.; Teng, N. N. H.; Sunwoo, J. B.; Alizadeh, A. A.; Clarke, M. F.; Weissman, I. L. The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. Proc. Natl. Acad. Sci. U. S. A. 2012 , 109 , 6662−6667..

Zheng, C.; Zhao, X.; Wang, Y.; Zhao, Y.; Zheng, Y.; Zhang, Z.; Liu, Q.; Liu, Y.; Shi, L. Immune modulating nanoparticles depleting tumor-associated macrophages to enhance immune checkpoint blockade therapy. Chem. Eng. J. 2022 , 435 , 134779..

Zhang, W.; Yuan, S.; Zhang, Z.; Fu, S.; Liu, S.; Liu, J.; Ma, Q.; Xia, Z.; Gu, P.; Gao, S.; Zhang, Z.; Zhang, X.; Liu, Y.; Zhang, N. Regulating tumor cells to awaken T cell antitumor function and enhance melanoma immunotherapy. Biomaterials 2025 , 316 , 123034..

Xu, G.; Chen, S.; Yang, H.; Feng, X.; Li, F.; Zhao, H.; Sun, L.; Yan, P.; Chen, Y.; Guo, G.; Sun, W.; Song, W.; Chen, Z.-S.; Wei, L.; Zhong, W. An ER stress and mitochondrial apoptosis Co-inducer for enhanced cancer immunotherapy. Cancer Lett. 2025 , 612 , 217485..

Huang, K. C. Y.; Chiang, S. F.; Lin, P. C.; Hong, W. Z.; Yang, P. C.; Chang, H. P.; Peng, S. L.; Chen, T. W.; Ke, T. W.; Liang, J. A.; Chen, W. T. L.; Chao, K. S. C. TNFα modulates PANX1 activation to promote ATP release and enhance P2RX7-mediated antitumor immune responses after chemotherapy in colorectal cancer. Cell Death Dis. 2024 , 15 , 24..

Li, Y.; Zhang, X.; Wan, X.; Liu, X.; Pan, W.; Li, N.; Tang, B. Inducing endoplasmic reticulum stress to expose immunogens: a DNA tetrahedron nanoregulator for enhanced immunotherapy. Adv. Funct. Mater. 2020 , 30 , 2000532..

[Zhang, Z.; Pan, Z.; Li, Q.; Huang, Q.; Shi, L.; Liu, Y. Rational design of ICD-inducing nanoparticles for cancer immunotherapy. Sci. Adv. 10 , eadk0716.

Ji, S.; Li, J.; Duan, X.; Zhang, J.; Zhang, Y.; Song, M.; Li, S.; Chen, H.; Ding, D. Targeted enrichment of enzyme-instructed assemblies in cancer cell lysosomes turns immunologically cold tumors hot. Angew. Chem., Int. Ed. 2021 , 60 , 26994−27004..

Xing, Y.; Yang, J.; Peng, A.; Qian, Y.; Liu, Y.; Pan, P.; Liu, Q. Lysosome targeted nanoparticle aggregation reverses immunosuppressive tumor microenvironment for cancer immunotherapy. Adv. Mater. 2024 , 36 , 2412730..

Lin, M. J.; Svensson-Arvelund, J.; Lubitz, G. S.; Marabelle,A.; Melero, I.; Brown, B. D.; Brody, J. D. Cancer vaccines: the next immunotherapy frontier. Nat. Cancer 2022 , 3 , 911−926..

Li, X.; Cai, X.; Zhang, Z.; Ding, Y.; Ma, R.; Huang, F.; Liu, Y.; Liu, J.; Shi, L. Mimetic heat shock protein mediated immune process to enhance cancer immunotherapy. Nano Lett. 2020 , 20 , 4454−4463..

Wittrup, K. D. Antitumor antibodies can drive therapeutic T cell responses. Trends Cancer 2017 , 3 , 615−620..

Zhao, Y.; Hou, X.; Chai, J.; Zhang, Z.; Xue, X.; Huang, F.; Liu, J.; Shi, L.; Liu, Y. Stapled liposomes enhance cross-priming of radio-immunotherapy. Adv. Mater. 2022 , 34 , 2107161..

Gajewski, T. F.; Schreiber, H.; Fu, Y. X. Innate and adaptive immune cells in the tumor microenvironment. Nat. Immunol. 2013 , 14 , 1014−1022..

Peng, S.; Lin, A.;Jiang, A.; Zhang, C.; Zhang, J.; Cheng, Q.; Luo, P.; Bai, Y. CTLs heterogeneity and plasticity: implications for cancer immunotherapy. Mol. Cancer 2024 , 23 , 58..

Janicki, C. N.; Jenkinson, S. R.; Williams, N. A.; Morgan, D. J. Loss of CTL Function among high-avidity tumor-specific CD8+ T cells following tumor infiltration. Cancer Res. 2008 , 68 , 2993−3000..

Li, X.; Shao, C.; Sh i, Y.; Han, W. Lessons learned from the blockade of immune checkpoints in cancer immunotherapy. J. Hematol. Oncol. 2018 , 11 , 31..

Keir, M. E.; Butte, M. J.; Freeman, G. J.; Sharpe, A. H. PD-1 and its ligands in tolerance and immunity. Annu. Rev. Immunol. 2008 , 26 , 677−704..

Zheng, Y.; Zhang, Z.; Liu, Q.; Zhao, Y.; Zheng, C.; Hao, J.; Yi, K.; Wang, Y.; Wang, C.; Zhao, X.; Shi, L.; Kang, C.; Liu, Y. Multifunctional nanomodulators regulate multiple pathways to enhance antitumor immunity. ACS Appl. Bio Mater. 2020 , 3 , 4635−4642..

Wang, X.; Yu, B.; Cao, B.; Zhou, J.; Deng, Y.; Wang, Z.; Jin, G. A chemical conjugation of JQ-1 and a TLR7 agonist induces tumoricidal effects in a murine model of melanoma via enhanced immunomodulation. Int. J. Cancer 2021 , 148 , 437−447..

Labadie, B. W.; Bao, R.; Luke, J. J. Reimagining IDO pathway inhibition in cancer immunotherapy via downstream focus on the tryptophan–kynurenine–aryl hydrocarbon axis. Clin. Cancer Res. 2019 , 25 , 1462−1471..

Cao, X.; Feng, N.; Huang, Q.; Zhang, Z.; Zhao, Y.; Li, Q.; Xiao, J.; Liu, Y. Nano-immunomodulators for multi-pathway regulation of immunosuppressive microenvironment of colorectal cancer. Chem. Eng. J. 2025 , 508 , 161104..

Hinshaw, D. C.; Shevde, L. A. The Tumor Microenvironment innately modulates cancer progression. Cancer Res. 2019 , 79 , 4557−4566..

Gu, Y.; Zhao, Y.; Zhang, Z.; Hao, J.; Zheng, Y.; Liu, Q.; Liu, Y.; Shi, L. An antibody-like polymeric nanoparticle removes intratumoral galectin-1 to enhance antitumor t-cell responses in cancer immunotherapy. ACS Appl. Mater. Interfaces 2021 , 13 , 22159−22168..

Xing, Y.; Li, J.; Wang, L.; Zhu, Z.; Yan, J.; Liu, Y.; Liu, Q. A Bifunctional lysosome-targeting chimera nanoplatform for tumor-selective protein degradation and enhanced cancer immunotherapy. Adv. Mater. 2025 , 37 , 2417942..

Sharma, P.; Hu-Lieskovan, S.; Wargo, J. A.; Ribas, A. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell 2017 , 168 , 707−723..

Dhainaut, M.; Rose, S. A.; Akturk, G.; Wroblewska, A.; Nielsen, S. R.; Park, E. S.; Buckup, M.; Roudko, V.; Pia, L.; Sweeney, R.; Le Berichel, J.; Wilk, C. M.; Bektesevic, A.; Lee, B. H.; Bhardwaj, N.; Rahman, A. H.; Baccarini, A.; Gnjatic, S.; Pe’er, D.; Merad, M.; Brown, B. D. Spatial CRISPR genomics identifies regulators of the tumor microenvironment. Cell 2022 , 185 , 1223−1239.e20..

Xing, Y.; Yang, J.; Wang, C.; Kang, Z.; Pan, Z.; Tang, J.; Li, F.; Wang, X.; Meng, X.-m.; Cheng, Z.; Liu, Y.; Liu, Q. Time-programmed activation of CD47 disruption and immunogenic cell death with Cas9 ribonucleoprotein nanocapsule for improved cancer immunotherapy. Chem. Eng. J. 2023 , 474 , 145796..

Zhang, Z.; Wang, Q.; Liu, Q.; Zheng, Y.; Zheng, C.; Yi, K.; Zhao, Y.; Gu, Y.; Wang, Y.; Wang, C.; Zhao, X.; Shi, L.; Kang, C.; Liu, Y. Dual-locking nanoparticles disrupt the PD-1/PD-L1 pathway for efficient cancer immunotherapy. Adv. Mater. 2019 , 31 , 1905751..

Mahas, A.; Neal Stewart, C.; Mahfouz, M. M. Harnessing CRISPR/Cas systems for programmable transcriptional and post-transcriptional regulation. Biotechnol. Adv. 2018 , 36 , 295−310..

Xing, Y.; Yang, J.; Wang, Y.; Wang, C.; Pan, Z.; Liu, F. L.; Liu, Y.; Liu, Q. Remodeling tumor immunogenicity with dual-activatable binary CRISPR nanomedicine for cancer immunotherapy. ACS Nano 2023 , 17 , 5713−5726..

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