REFERENCES

1. Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992;11:3887-95.

2. Nishimura H, Nose M, Hiai H, Minato N, Honjo T. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity. 1999;11:141-51.

3. Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999;5:1365-9.

4. Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192:1027-34.

5. Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8:793-800.

6. Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A. 2002;99:12293-7.

7. Curiel TJ, Wei S, Dong H, et al. Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med. 2003;9:562-7.

8. Morad G, Helmink BA, Sharma P, Wargo JA. Hallmarks of response, resistance, and toxicity to immune checkpoint blockade. Cell. 2022;185:576.

9. Conforti F, Pala L, Di Mitri D, et al. Sex hormones, the anticancer immune response, and therapeutic opportunities. Cancer Cell. 2025;43:343-60.

10. Cortellini A, Bersanelli M, Buti S, et al. A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors: when overweight becomes favorable. J Immunother Cancer. 2019;7:57.

11. Blake SJ, Wolf Y, Boursi B, Lynn DJ. Role of the microbiota in response to and recovery from cancer therapy. Nat Rev Immunol. 2024;24:308-25.

12. Keam SJ. Cadonilimab: first approval. Drugs. 2022;82:1333-9.

13. Dhillon S. Ivonescimab: first approval. Drugs. 2024;84:1135-42.

14. Paik J. Nivolumab plus relatlimab: first approval. Drugs. 2022;82:925-31.

15. Keam SJ. Iparomlimab and tuvonralimab: first approval. Drugs. 2025;85:699-706.

16. KEYTRUDA® (pembrolizumab) injection, for intravenous use. 2014. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/125514s172lbl.pdf. [Last accessed on 11 May 2026].

17. TECENTRIQ® (atezolizumab) injection, for intravenous use. 2016. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761034s053lbl.pdf. [Last accessed on 11 May 2026].

18. Zhao S, Zhao H, Yang W, Zhang L. The next generation of immunotherapies for lung cancers. Nat Rev Clin Oncol. 2025;22:592-616.

19. Laktionov K, Smolin A, Stroyakovskiy D, et al. Prolgolimab with chemotherapy as first-line treatment for advanced non-squamous non-small-cell lung cancer. Eur J Cancer. 2025;217:115255.

20. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229-63.

21. Mao Y, Xie H, Lv M, et al. The landscape of objective response rate of anti-PD-1/L1 monotherapy across 31 types of cancer: a system review and novel biomarker investigating. Cancer Immunol Immunother. 2023;72:2483-98.

22. Lang R, Welponer T, Richtig E, et al. Nivolumab for locally advanced and metastatic cutaneous squamous cell carcinoma (NIVOSQUACS study)-Phase II data covering impact of concomitant haematological malignancies. J Eur Acad Dermatol Venereol. 2023;37:1799-810.

23. Kaufman HL, Russell JS, Hamid O, et al. Updated efficacy of avelumab in patients with previously treated metastatic Merkel cell carcinoma after ≥1 year of follow-up: JAVELIN Merkel 200, a phase 2 clinical trial. J Immunother Cancer. 2018;6:7.

24. Yau T, Park JW, Finn RS, et al. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2022;23:77-90.

25. Klein C, Brinkmann U, Reichert JM, Kontermann RE. The present and future of bispecific antibodies for cancer therapy. Nat Rev Drug Discov. 2024;23:301-19.

26. Finn RS, Qin S, Ikeda M, et al.; IMbrave150 Investigators. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382:1894-905.

27. Reck M, Mok TSK, Nishio M, et al.; IMpower150 Study Group. Atezolizumab plus bevacizumab and chemotherapy in non-small-cell lung cancer (IMpower150): key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised, open-label phase 3 trial. Lancet Respir Med. 2019;7:387-401.

28. Douma LAH, van der Noort V, Lalezari F, et al. Pembrolizumab plus lenvatinib as second-line treatment in patients with pleural mesothelioma (PEMMELA): cohort 2 of a single-arm, phase 2 study. Lancet Oncol. 2025;26:1676-84.

29. Motzer RJ, Jonasch E, Agarwal N, et al. NCCN Guidelines® Insights: kidney cancer, version 2.2024. J Natl Compr Canc Netw. 2024;22:4-16.

30. Xiong A, Wang L, Chen J, et al. Ivonescimab versus pembrolizumab for PD-L1-positive non-small cell lung cancer (HARMONi-2): a randomised, double-blind, phase 3 study in China. Lancet. 2025;405:839-49.

31. Chen Z, Yang F, Jiang Z, et al. Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (HARMONi-6): a randomised, double-blind, phase 3 trial. Lancet. 2025;406:2078-88.

32. Johnson ML, Cho BC, Luft A, et al.; POSEIDON investigators. Durvalumab with or without tremelimumab in combination with chemotherapy as first-line therapy for metastatic non-small-cell lung cancer: the phase III POSEIDON study. J Clin Oncol. 2023;41:1213-27.

33. Paz-Ares L, Ciuleanu TE, Cobo M, et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22:198-211.

34. Tawbi HA, Schadendorf D, Lipson EJ, et al.; RELATIVITY-047 Investigators. Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma. N Engl J Med. 2022;386:24-34.

35. Merck KGaA, Darmstadt, Germany Statement on phase II study of Bintrafusp Alfa in first-line treatment of biliary tract cancer. Available from: https://www.emdgroup.com/en/news/bintrafusp-alfa-update-23-08-2021.html. [Last accessed on 11 May 2026].

36. Cho BC, Lee JS, Wu YL, et al. Bintrafusp Alfa versus pembrolizumab in patients with treatment-naive, programmed death-ligand 1-high advanced NSCLC: a randomized, open-label, phase 3 trial. J Thorac Oncol. 2023;18:1731-42.

37. Masuda J, Sakai H, Tsurutani J, et al. Efficacy, safety, and biomarker analysis of nivolumab in combination with abemaciclib plus endocrine therapy in patients with HR-positive HER2-negative metastatic breast cancer: a phase II study (WJOG11418B NEWFLAME trial). J Immunother Cancer. 2023;11:e007126.

38. Spigel D, Jotte R, Nemunaitis J, et al. Randomized phase 2 studies of checkpoint inhibitors alone or in combination with pegilodecakin in patients with metastatic NSCLC (CYPRESS 1 and CYPRESS 2). J Thorac Oncol. 2021;16:327-33.

39. Levy BP, Giaccone G, Besse B, et al. Randomised phase 2 study of pembrolizumab plus CC-486 versus pembrolizumab plus placebo in patients with previously treated advanced non-small cell lung cancer. Eur J Cancer. 2019;108:120-8.

40. Wang ZQ, Zhang ZC, Wu YY, et al. Bromodomain and extraterminal (BET) proteins: biological functions, diseases, and targeted therapy. Signal Transduct Target Ther. 2023;8:420.

41. Nassiri F, Patil V, Yefet LS, et al. Oncolytic DNX-2401 virotherapy plus pembrolizumab in recurrent glioblastoma: a phase 1/2 trial. Nat Med. 2023;29:1370-8.

42. Liu S, Li F, Ma Q, et al. OX40L-armed oncolytic virus boosts T-cell response and remodels tumor microenvironment for pancreatic cancer treatment. Theranostics. 2023;13:4016-29.

43. Zhang P, Rashidi A, Zhao J, et al. STING agonist-loaded, CD47/PD-L1-targeting nanoparticles potentiate antitumor immunity and radiotherapy for glioblastoma. Nat Commun. 2023;14:1610.

44. Tsuchikama K, Anami Y, Ha SYY, Yamazaki CM. Exploring the next generation of antibody-drug conjugates. Nat Rev Clin Oncol. 2024;21:203-23.

45. Rongvaux A, Jackson R, Harman CC, et al. Apoptotic caspases prevent the induction of type I interferons by mitochondrial DNA. Cell. 2014;159:1563-77.

46. Conche C, Finkelmeier F, Pešić M, et al. Combining ferroptosis induction with MDSC blockade renders primary tumours and metastases in liver sensitive to immune checkpoint blockade. Gut. 2023;72:1774-82.

47. Tao Q, Liu N, Wu J, Chen J, Chen X, Peng C. Mefloquine enhances the efficacy of anti-PD-1 immunotherapy via IFN-γ-STAT1-IRF1-LPCAT3-induced ferroptosis in tumors. J Immunother Cancer. 2024;12:e008554.

48. Gong D, Chen M, Wang Y, Shi J, Hou Y. Role of ferroptosis on tumor progression and immunotherapy. Cell Death Discov. 2022;8:427.

49. He Z, Zheng D, Li F, et al. TMOD3 accelerated resistance to immunotherapy in KRAS-mutated pancreatic cancer through promoting autophagy-dependent degradation of ASCL4. Drug Resist Updat. 2025;78:101171.

50. Zhou X, Zou L, Liao H, et al. Abrogation of HnRNP L enhances anti-PD-1 therapy efficacy via diminishing PD-L1 and promoting CD8+ T cell-mediated ferroptosis in castration-resistant prostate cancer. Acta Pharm Sin B. 2022;12:692-707.

51. Catanzaro E, Demuynck R, Naessens F, Galluzzi L, Krysko DV. Immunogenicity of ferroptosis in cancer: a matter of context? Trends Cancer. 2024;10:407-16.

52. Wiernicki B, Maschalidi S, Pinney J, et al. Cancer cells dying from ferroptosis impede dendritic cell-mediated anti-tumor immunity. Nat Commun. 2022;13:3676.

53. Ma X, Xiao L, Liu L, et al. CD36-mediated ferroptosis dampens intratumoral CD8+ T cell effector function and impairs their antitumor ability. Cell Metab. 2021;33:1001-12.e5.

54. Gao Z, Zhang J, Hou Y, et al. Boosting the synergism between cancer ferroptosis and immunotherapy via targeted stimuli-responsive liposomes. Biomaterials. 2024;305:122442.

55. Wu B, Yang X, Kong N, Liang J, Li S, Wang H. Engineering modular peptide nanoparticles for ferroptosis-enhanced tumor immunotherapy. Angew Chem Int Ed Engl. 2025;64:e202421703.

56. Yan C, Liu Y, Zhao G, et al. Inhalable metal-organic framework-mediated cuproptosis combined with PD-L1 checkpoint blockade for lung metastasis synergistic immunotherapy. Acta Pharm Sin B. 2024;14:2281-97.

57. Ribas A, Medina T, Kirkwood JM, et al. Overcoming PD-1 blockade resistance with CpG-A Toll-like receptor 9 agonist vidutolimod in patients with metastatic melanoma. Cancer Discov. 2021;11:2998-3007.

58. Curigliano G, Jimenez MM, Shimizu T, et al. A phase I trial of LHC165 single agent and in combination with spartalizumab in patients with advanced solid malignancies. ESMO Open. 2024;9:103643.

59. Yu X, Long Y, Chen B, et al. PD-L1/TLR7 dual-targeting nanobody-drug conjugate mediates potent tumor regression via elevating tumor immunogenicity in a host-expressed PD-L1 bias-dependent way. J Immunother Cancer. 2022;10:e004590.

60. Braun DA, Moranzoni G, Chea V, et al. A neoantigen vaccine generates antitumour immunity in renal cell carcinoma. Nature. 2025;639:474-82.

61. Weber JS, Carlino MS, Khattak A, et al. Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): a randomised, phase 2b study. Lancet. 2024;403:632-44.

62. Sánchez-Paulete AR, Cueto FJ, Martínez-López M, et al. Cancer immunotherapy with immunomodulatory anti-CD137 and anti-PD-1 monoclonal antibodies requires BATF3-dependent dendritic cells. Cancer Discov. 2016;6:71-9.

63. Zhou J, Tison K, Zhou H, et al. STAT5 and STAT3 balance shapes dendritic cell function and tumour immunity. Nature. 2025;643:519-28.

64. Jiang Y, Zheng Y, Zhang YW, et al. Reciprocal inhibition between TP63 and STAT1 regulates anti-tumor immune response through interferon-γ signaling in squamous cancer. Nat Commun. 2024;15:2484.

65. Khushalani NI, Ott PA, Ferris RL, et al. Final results of urelumab, an anti-CD137 agonist monoclonal antibody, in combination with cetuximab or nivolumab in patients with advanced solid tumors. J Immunother Cancer. 2024;12:e007364.

66. Majocchi S, Lloveras P, Nouveau L, et al. NI-3201 is a bispecific antibody mediating PD-L1-dependent CD28 co-stimulation on T cells for enhanced tumor control. Cancer Immunol Res. 2025;13:365-83.

67. Yang Z, Liu X, Zhu J, et al. Inhibiting intracellular CD28 in cancer cells enhances antitumor immunity and overcomes anti-PD-1 resistance via targeting PD-L1. Cancer Cell. 2025;43:86-102.e10.

68. Hwang BJ, Tsao LC, Acharya CR, et al. Sensitizing immune unresponsive colorectal cancers to immune checkpoint inhibitors through MAVS overexpression. J Immunother Cancer. 2022;10:e003721.

69. Zhuang Q, Dai Z, Xu X, et al. RNA methyltransferase FTSJ3 regulates the type I interferon pathway to promote hepatocellular carcinoma immune evasion. Cancer Res. 2024;84:405-18.

70. Bule P, Aguiar SI, Aires-Da-Silva F, Dias JNR. Chemokine-directed tumor microenvironment modulation in cancer immunotherapy. Int J Mol Sci. 2021;22:9804.

71. Yang L, Li A, Yu W, et al. Blockade of purine metabolism reverses macrophage immunosuppression and enhances anti-tumor immunity in non-small cell lung cancer. Drug Resist Updat. 2025;78:101175.

72. Doi T, Muro K, Ishii H, et al. A phase I study of the anti-CC chemokine receptor 4 antibody, mogamulizumab, in combination with nivolumab in patients with advanced or metastatic solid tumors. Clin Cancer Res. 2019;25:6614-22.

73. Bockorny B, Semenisty V, Macarulla T, et al. BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: the COMBAT trial. Nat Med. 2020;26:878-85.

74. Bergeron P, Dos Santos M, Sitterle L, et al. Non-homogenous intratumor ionizing radiation doses synergize with PD1 and CXCR2 blockade. Nat Commun. 2024;15:8845.

75. Jie X, Chen Y, Zhao Y, et al. Targeting KDM4C enhances CD8+ T cell mediated antitumor immunity by activating chemokine CXCL10 transcription in lung cancer. J Immunother Cancer. 2022;10:e003716.

76. Jiang W, Guan B, Sun H, et al. WNT11 promotes immune evasion and resistance to anti-PD-1 therapy in liver metastasis. Nat Commun. 2025;16:1429.

77. Lee HJ, Song KH, Oh SJ, et al. Targeting TCTP sensitizes tumor to T cell-mediated therapy by reversing immune-refractory phenotypes. Nat Commun. 2022;13:2127.

78. An D, Chen G, Cheng WY, et al. LTβR agonism promotes antitumor immune responses via modulation of the tumor microenvironment. Cancer Res. 2024;84:3984-4001.

79. Plaschka M, Benboubker V, Grimont M, et al. ZEB1 transcription factor promotes immune escape in melanoma. J Immunother Cancer. 2022;10:e003484.

80. Kuo HY, Khan KA, Kerbel RS. Antiangiogenic-immune-checkpoint inhibitor combinations: lessons from phase III clinical trials. Nat Rev Clin Oncol. 2024;21:468-82.

81. Rapisarda A, Melillo G. Overcoming disappointing results with antiangiogenic therapy by targeting hypoxia. Nat Rev Clin Oncol. 2012;9:378-90.

82. Arjaans M, Schröder CP, Oosting SF, Dafni U, Kleibeuker JE, de Vries EG. VEGF pathway targeting agents, vessel normalization and tumor drug uptake: from bench to bedside. Oncotarget. 2016;7:21247-58.

83. Guelfi S, Hodivala-Dilke K, Bergers G. Targeting the tumour vasculature: from vessel destruction to promotion. Nat Rev Cancer. 2024;24:655-75.

84. Huang Y, Yuan J, Righi E, et al. Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy. Proc Natl Acad Sci U S A. 2012;109:17561-6.

85. Lan J, Zeng R, Li Z, et al. Biomimetic nanomodulators with synergism of photothermal therapy and vessel normalization for boosting potent anticancer immunity. Adv Mater. 2024;36:e2408511.

86. Schmittnaegel M, Rigamonti N, Kadioglu E, et al. Dual angiopoietin-2 and VEGFA inhibition elicits antitumor immunity that is enhanced by PD-1 checkpoint blockade. Sci Transl Med. 2017;9:eaak9670.

87. Liu Y, Zhan Z, Kang Z, et al. Preclinical and early clinical studies of a novel compound SYHA1813 that efficiently crosses the blood-brain barrier and exhibits potent activity against glioblastoma. Acta Pharm Sin B. 2023;13:4748-64.

88. Zhang Y, Fang Z, Pan D, et al. Dendritic polymer-based nanomedicines remodel the tumor stroma: improve drug penetration and enhance antitumor immune response. Adv Mater. 2024;36:e2401304.

89. Gan L, Lu T, Lu Y, et al. Endosialin-positive CAFs promote hepatocellular carcinoma progression by suppressing CD8+ T cell infiltration. J Immunother Cancer. 2024;12:e009111.

90. Saatci O, Kaymak A, Raza U, et al. Targeting lysyl oxidase (LOX) overcomes chemotherapy resistance in triple negative breast cancer. Nat Commun. 2020;11:2416.

91. Lee CJ, Jang TY, Jeon SE, et al. The dysadherin/MMP9 axis modifies the extracellular matrix to accelerate colorectal cancer progression. Nat Commun. 2024;15:10422.

92. Sun X, Wu B, Chiang HC, et al. Tumour DDR1 promotes collagen fibre alignment to instigate immune exclusion. Nature. 2021;599:673-8.

93. Zhang G, Guo L, Yang C, et al. A novel role of breast cancer-derived hyaluronan on inducement of M2-like tumor-associated macrophages formation. Oncoimmunology. 2016;5:e1172154.

94. Blair AB, Wang J, Davelaar J, et al. Dual stromal targeting sensitizes pancreatic adenocarcinoma for anti-programmed cell death protein 1 therapy. Gastroenterology. 2022;163:1267-80.e7.

95. Ishihara J, Fukunaga K, Ishihara A, et al. Matrix-binding checkpoint immunotherapies enhance antitumor efficacy and reduce adverse events. Sci Transl Med. 2017;9:eaan0401.

96. Bhandari C, Moffat A, Shah N, et al. PD-L1 immune checkpoint targeted photoactivable liposomes (iTPALs) prime the stroma of pancreatic tumors and promote self-delivery. Adv Healthc Mater. 2024;13:e2304340.

97. Fattori S, Le Roy A, Houacine J, et al. CD25high effector regulatory T cells hamper responses to PD-1 blockade in triple-negative breast cancer. Cancer Res. 2023;83:3026-44.

98. Redin E, Garmendia I, Lozano T, et al. SRC family kinase (SFK) inhibitor dasatinib improves the antitumor activity of anti-PD-1 in NSCLC models by inhibiting Treg cell conversion and proliferation. J Immunother Cancer. 2021;9:e001496.

99. Meng Y, Ye F, Nie P, et al. Immunosuppressive CD10+ALPL+ neutrophils promote resistance to anti-PD-1 therapy in HCC by mediating irreversible exhaustion of T cells. J Hepatol. 2023;79:1435-49.

100. DeNardo DG, Ruffell B. Macrophages as regulators of tumour immunity and immunotherapy. Nat Rev Immunol. 2019;19:369-82.

101. Larroquette M, Guegan JP, Besse B, et al. Spatial transcriptomics of macrophage infiltration in non-small cell lung cancer reveals determinants of sensitivity and resistance to anti-PD1/PD-L1 antibodies. J Immunother Cancer. 2022;10:e003890.

102. Cousin S, Guégan JP, Shitara K, et al. Identification of microenvironment features associated with primary resistance to anti-PD-1/PD-L1 + antiangiogenesis in gastric cancer through spatial transcriptomics and plasma proteomics. Mol Cancer. 2024;23:197.

103. Ajith A, Mamouni K, Horuzsko DD, et al. Targeting TREM1 augments antitumor T cell immunity by inhibiting myeloid-derived suppressor cells and restraining anti-PD-1 resistance. J Clin Invest. 2023;133:e167951.

104. Prasad M, Zorea J, Jagadeeshan S, et al. MEK1/2 inhibition transiently alters the tumor immune microenvironment to enhance immunotherapy efficacy against head and neck cancer. J Immunother Cancer. 2022;10:e003917.

105. Voissière A, Gomez-Roca C, Chabaud S, et al. The CSF-1R inhibitor pexidartinib affects FLT3-dependent DC differentiation and may antagonize durvalumab effect in patients with advanced cancers. Sci Transl Med. 2024;16:eadd1834.

106. Yue T, Li J, Zhu J, et al. Hydrogen sulfide creates a favorable immune microenvironment for colon cancer. Cancer Res. 2023;83:595-612.

107. Boelaars K, Goossens-Kruijssen L, Wang D, et al. Unraveling the impact of sialic acids on the immune landscape and immunotherapy efficacy in pancreatic cancer. J Immunother Cancer. 2023;11:e007805.

108. Bell HN, Huber AK, Singhal R, et al. Microenvironmental ammonia enhances T cell exhaustion in colorectal cancer. Cell Metab. 2023;35:134-49.e6.

109. Zhang J, Wang S, Guo X, et al. Arginine supplementation targeting tumor-killing immune cells reconstructs the tumor microenvironment and enhances the antitumor immune response. ACS Nano. 2022;16:12964-78.

110. Zang J, Yang Y, Zheng X, et al. Dynamic tagging to drive arginine nano-assembly to metabolically potentiate immune checkpoint blockade therapy. Biomaterials. 2023;292:121938.

111. Jin XK, Zhang SM, Liang JL, et al. A PD-L1-targeting regulator for metabolic reprogramming to enhance glutamine inhibition-mediated synergistic antitumor metabolic and immune therapy. Adv Mater. 2024;36:e2309094.

112. Wang W, Zheng H, Jiang J, et al. Engineering micro oxygen factories to slow tumour progression via hyperoxic microenvironments. Nat Commun. 2022;13:4495.

113. Chen N, Li Z, Liu H, et al. Enhancing PD-1 blockade in NSCLC: reprogramming tumor immune microenvironment with albumin-bound statins targeting lipid rafts and mitochondrial respiration. Bioact Mater. 2025;49:140-53.

114. Liu X, Bao X, Hu M, et al. Inhibition of PCSK9 potentiates immune checkpoint therapy for cancer. Nature. 2020;588:693-8.

115. Li L, Zeng X, Chao Z, et al. Targeting Alpha-ketoglutarate disruption overcomes immunoevasion and improves PD-1 blockade immunotherapy in renal cell carcinoma. Adv Sci. 2023;10:e2301975.

116. Zheng X, Chen J, Deng M, et al. G3BP1 and SLU7 jointly promote immune evasion by downregulating MHC-I via PI3K/Akt activation in bladder cancer. Adv Sci. 2024;11:e2305922.

117. Cheng C, Zha Q, Sun L, et al. VCP downstream metabolite glycerol-3-phosphate (G3P) inhibits CD8+T cells function in the HCC microenvironment. Signal Transduct Target Ther. 2025;10:26.

118. Grosser R, Cherkassky L, Chintala N, Adusumilli PS. Combination immunotherapy with CAR T cells and checkpoint blockade for the treatment of solid tumors. Cancer Cell. 2019;36:471-82.

119. Giuffrida L, Sek K, Henderson MA, et al. IL-15 preconditioning augments CAR T cell responses to checkpoint blockade for improved treatment of solid tumors. Mol Ther. 2020;28:2379-93.

120. Hegewisch-Becker S, Mendez G, Chao J, et al. First-line nivolumab and relatlimab plus chemotherapy for gastric or gastroesophageal junction adenocarcinoma: the phase II RELATIVITY-060 study. J Clin Oncol. 2024;42:2080-93.

121. Son W, Lee Y, Park Y, et al. Fc-competent TIGITx4-1BB bispecific antibody exerts potent long-lasting antitumor activity by potentiating CD8+ T cell activity and Fcγ receptor-mediated modulation of the tumor microenvironment. J Immunother Cancer. 2025;13:e010728.

122. Hu Y, Paris S, Bertolet G, et al. Combining a nanoparticle-mediated immunoradiotherapy with dual blockade of LAG3 and TIGIT improves the treatment efficacy in anti-PD1 resistant lung cancer. J Nanobiotechnology. 2022;20:417.

123. Dolan M, Libby KA, Ringel AE, van Galen P, McAllister SS. Ageing, immune fitness and cancer. Nat Rev Cancer. 2025;25:848-72.

124. Anobile DP, Salaroglio IC, Tabbò F, et al. Autocrine 17-β-estradiol/estrogen receptor-α loop determines the response to immune checkpoint inhibitors in non-small cell lung cancer. Clin Cancer Res. 2023;29:3958-73.

125. Chakraborty B, Byemerwa J, Shepherd J, et al. Inhibition of estrogen signaling in myeloid cells increases tumor immunity in melanoma. J Clin Invest. 2021;131:e151347.

126. Adurthi S, Kumar MM, Vinodkumar HS, et al. Oestrogen receptor-α binds the FOXP3 promoter and modulates regulatory T-cell function in human cervical cancer. Sci Rep. 2017;7:17289.

127. Svoronos N, Perales-Puchalt A, Allegrezza MJ, et al. Tumor cell-independent estrogen signaling drives disease progression through mobilization of myeloid-derived suppressor cells. Cancer Discov. 2017;7:72-85.

128. Milette S, Hashimoto M, Perrino S, et al. Sexual dimorphism and the role of estrogen in the immune microenvironment of liver metastases. Nat Commun. 2019;10:5745.

129. Artham S, Juras PK, Goyal A, et al. Estrogen signaling suppresses tumor-associated tissue eosinophilia to promote breast tumor growth. Sci Adv. 2024;10:eadp2442.

130. Kwon Y. Potential pro-tumorigenic effect of bisphenol A in breast cancer via altering the tumor microenvironment. Cancers. 2022;14:3021.

131. Klinge CM. Estrogenic control of mitochondrial function. Redox Biol. 2020;31:101435.

132. Yuan B, Clark CA, Wu B, et al. Estrogen receptor beta signaling in CD8+ T cells boosts T cell receptor activation and antitumor immunity through a phosphotyrosine switch. J Immunother Cancer. 2021;9:e001932.

133. Guan X, Polesso F, Wang C, et al. Androgen receptor activity in T cells limits checkpoint blockade efficacy. Nature. 2022;606:791-6.

134. Kwon H, Schafer JM, Song NJ, et al. Androgen conspires with the CD8+ T cell exhaustion program and contributes to sex bias in cancer. Sci Immunol. 2022;7:eabq2630.

135. Liu Q, You B, Meng J, et al. Targeting the androgen receptor to enhance NK cell killing efficacy in bladder cancer by modulating ADAR2/circ_0001005/PD-L1 signaling. Cancer Gene Ther. 2022;29:1988-2000.

136. Jin WB, Xiao L, Jeong M, et al.; JRI IBD Live Cell Bank Consortium. Microbiota-derived bile acids antagonize the host androgen receptor and drive anti-tumor immunity. Cell. 2025;188:2336-53.e38.

137. Madi A, Shi H, Su M, et al. DGAT1 mediates sex-specific CD8+ T cell antitumour responses. Nat Metab. 2026;8:685-703.

138. Zitvogel L, Fidelle M, Kroemer G. Long-distance microbial mechanisms impacting cancer immunosurveillance. Immunity. 2024;57:2013-29.

139. Sivan A, Corrales L, Hubert N, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015;350:1084-9.

140. Fidelle M, Rauber C, Alves Costa Silva C, et al. A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers. Science. 2023;380:eabo2296.

141. Park JS, Gazzaniga FS, Wu M, et al. Targeting PD-L2-RGMb overcomes microbiome-related immunotherapy resistance. Nature. 2023;617:377-85.

142. Najar TA, Hao Y, Hao Y, et al. Microbiota-induced T cell plasticity enables immune-mediated tumour control. Nature. 2026;651:201-10.

143. Routy B, Le Chatelier E, Derosa L, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359:91-7.

144. Davar D, Dzutsev AK, McCulloch JA, et al. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. Science. 2021;371:595-602.

145. Zhou H, Sun R, Nie X, et al. A clinic-responder-derived defined microbial consortium enhances anti-PD-1 immunotherapy efficacy in mice. Nat Microbiol. 2026;11:993-1007.

146. Fu A, Yao B, Dong T, et al. Tumor-resident intracellular microbiota promotes metastatic colonization in breast cancer. Cell. 2022;185:1356-72.e26.

147. Sahler JM, Eade CR, Altier C, March JC. Salmonella enterica serovar typhimurium increases functional PD-L1 synergistically with gamma interferon in intestinal epithelial cells via Salmonella pathogenicity island 2. Infect Immun. 2018;86:e00674-17.

148. Wu YY, Lin CW, Cheng KS, et al. Increased programmed death-ligand-1 expression in human gastric epithelial cells in Helicobacter pylori infection. Clin Exp Immunol. 2010;161:551-9.

149. Hezaveh K, Shinde RS, Klötgen A, et al. Tryptophan-derived microbial metabolites activate the aryl hydrocarbon receptor in tumor-associated macrophages to suppress anti-tumor immunity. Immunity. 2022;55:324-40.e8.

150. Nejman D, Livyatan I, Fuks G, et al. The human tumor microbiome is composed of tumor type-specific intracellular bacteria. Science. 2020;368:973-80.

151. Chen J, Gao Y, Chen Y, et al. Identification and validation of intratumoral microbiome associated with sensitization to immune checkpoint inhibitors. Cell Rep Med. 2025;6:102306.

152. Canale FP, Basso C, Antonini G, et al. Metabolic modulation of tumours with engineered bacteria for immunotherapy. Nature. 2021;598:662-6.

153. Murphy S, Rahmy S, Gan D, et al. Ketogenic diet alters the epigenetic and immune landscape of prostate cancer to overcome resistance to immune checkpoint blockade therapy. Cancer Res. 2024;84:1597-612.

154. Fiuza-Luces C, Valenzuela PL, Gálvez BG, et al. The effect of physical exercise on anticancer immunity. Nat Rev Immunol. 2024;24:282-93.

155. Geng Q, Li L, Shen Z, et al. Norepinephrine inhibits CD8+ T-cell infiltration and function, inducing anti-PD-1 mAb resistance in lung adenocarcinoma. Br J Cancer. 2023;128:1223-35.

156. Qiao G, Chen M, Mohammadpour H, et al. Chronic adrenergic stress contributes to metabolic dysfunction and an exhausted phenotype in T cells in the tumor microenvironment. Cancer Immunol Res. 2021;9:651-64.

157. Yan X, Liu P, Li D, et al. Novel evidence for the prognostic impact of β-blockers in solid cancer patients receiving immune checkpoint inhibitors. Int Immunopharmacol. 2022;113:109383.

158. Zhu J, Naulaerts S, Boudhan L, Martin M, Gatto L, Van den Eynde BJ. Tumour immune rejection triggered by activation of α2-adrenergic receptors. Nature. 2023;618:607-15.

159. Yang J, Wu Y, Lv X, et al. Neurotransmitters: an emerging target for therapeutic resistance to tumor immune checkpoint inhibitors. Mol Cancer. 2025;24:216.

160. Schneider MA, Heeb L, Beffinger MM, et al. Attenuation of peripheral serotonin inhibits tumor growth and enhances immune checkpoint blockade therapy in murine tumor models. Sci Transl Med. 2021;13:eabc8188.

161. Balood M, Ahmadi M, Eichwald T, et al. Nociceptor neurons affect cancer immunosurveillance. Nature. 2022;611:405-12.

162. Amit M, Eichwald T, Roger A, et al. Neuro-immune cross-talk in cancer. Nat Rev Cancer. 2025;25:573-89.

Cancer Drug Resistance
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