Prognostic significance and immune escape implication of tumor-infiltrating neutrophil plasticity in human head and neck squamous cell carcinoma
Springer Science and Business Media LLC - Trang 1-15 - 2024
Tóm tắt
Tumor-infiltrating neutrophils play a crucial role in the progression of head and neck squamous cell carcinoma (HNSCC). Here, we aimed to statistically quantify the plasticity of HNSCC-infiltrating N2/N1 neutrophils and examine its impacts on survival and immune infiltration landscape. A retrospective study of 80 patients who underwent curative surgical resection for HNSCC between 2014 and 2017 was conducted in this study. HNSCC-infiltrating neutrophil phenotypes were classified using immunofluorescence staining, and the N2/N1 neutrophil plasticity was evaluated via the ratio of N2/N1 neutrophils. We then assessed the correlations between N2/N1 neutrophil plasticity, clinicopathological characteristics, and immune infiltration landscape using rigorous statistical methods. Infiltration variations of N1 and N2 neutrophils were observed between the tumor nest (TN) and tumor stroma (TS), with TN exhibiting higher N2 neutrophil infiltration and lower N1 neutrophil infiltration. High ratios of N2/N1 neutrophils were correlated with advanced TNM stage, large tumor size and invasion of adjacent tissue. High infiltration of N2 neutrophils was associated with decreased overall and relapse-free survival, which were opposite for N1 neutrophils. The independent prognostic role of N2/N1 neutrophil plasticity, particularly within the TN region, was confirmed by multivariate analyses. Moreover, the ratio of N2/N1 neutrophils within the TN region showed correlations with high CD8+ T cells infiltration and low FOXP3+ Tregs infiltration. We identify HNSCC-infiltrating N2/N1 neutrophil plasticity as a crucial prognostic indictor which potentially reflects the tumor microenvironment (TME) and immune escape landscape within HNSCC tissues. Further investigations and validations may provide novel therapeutic strategies for personalized immunomodulation in HNSCC patients.
Tài liệu tham khảo
Marur S, Forastiere AA. Head and neck squamous cell carcinoma: update on epidemiology, diagnosis, and treatment. Mayo Clin Proc. 2016;91(3):386–96. https://doi.org/10.1016/j.mayocp.2015.12.017.
Chow LQM. Head and neck cancer. N Engl J Med. 2020;382(1):60–72. https://doi.org/10.1056/NEJMra1715715.
Zhu X, Zhou J, Zhou L, Zhang M, Gao C, Tao L. Association between postoperative radiotherapy for young-onset head and neck cancer and long-term risk of second primary malignancy: a population-based study. J Transl Med. 2022;20(1):405. https://doi.org/10.1186/s12967-022-03544-y.
Choi JH, Lee BS, Jang JY, Lee YS, Kim HJ, Roh J, et al. Single-cell transcriptome profiling of the stepwise progression of head and neck cancer. Nat Commun. 2023;14(1):1055. https://doi.org/10.1038/s41467-023-36691-x.
Wang X, Muzaffar J, Kirtane K, Song F, Johnson M, Schell MJ, et al. T cell repertoire in peripheral blood as a potential biomarker for predicting response to concurrent cetuximab and nivolumab in head and neck squamous cell carcinoma. J Immunother Cancer. 2022;10(6): e004512. https://doi.org/10.1136/jitc-2022-004512.
Ruffin AT, Li H, Vujanovic L, Zandberg DP, Ferris RL, Bruno TC. Improving head and neck cancer therapies by immunomodulation of the tumour microenvironment. Nat Rev Cancer. 2023;23(3):173–88. https://doi.org/10.1038/s41568-022-00531-9.
Tang D, Zhang D, Heng Y, Zhu XK, Lin HQ, Zhou J, et al. Tumor-infiltrating PD-L1+ neutrophils induced by GM-CSF suppress T cell function in laryngeal squamous cell carcinoma and predict unfavorable prognosis. J Inflamm Res. 2022;15:1079–97. https://doi.org/10.2147/JIR.S347777.
Huang Q, Hsueh CY, Shen YJ, Guo Y, Huang JM, Zhang YF, et al. Small extracellular vesicle-packaged TGFβ1 promotes the reprogramming of normal fibroblasts into cancer-associated fibroblasts by regulating fibronectin in head and neck squamous cell carcinoma. Cancer Lett. 2021;517:1–13. https://doi.org/10.1016/j.canlet.2021.05.017.
Ferris RL, Licitra L. PD-1 immunotherapy for recurrent or metastatic HNSCC. Lancet. 2019;394(10212):1882–4. https://doi.org/10.1016/S0140-6736(19)32539-5.
Burtness B, Harrington KJ, Greil R, Soulières D, Tahara M, de Castro JG, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394(10212):1915–28. https://doi.org/10.1016/S0140-6736(19)32591-7.
Heng Y, Zhu X, Lin H, Jingyu M, Ding X, Tao L, et al. CD206+ tumor-associated macrophages interact with CD4+ tumor-infiltrating lymphocytes and predict adverse patient outcome in human laryngeal squamous cell carcinoma. J Transl Med. 2023;21(1):167. https://doi.org/10.1186/s12967-023-03910-4.
Sica A, Schioppa T, Mantovani A, Allavena P. Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer. 2006;42(6):717–27. https://doi.org/10.1016/j.ejca.2006.01.003.
Zhang D, Tang D, Heng Y, Zhu XK, Zhou L, Tao L, et al. Prognostic impact of tumor-infiltrating lymphocytes in laryngeal squamous cell carcinoma patients. Laryngoscope. 2021;131(4):E1249–55. https://doi.org/10.1002/lary.29196.
Valero C, Pardo L, López M, García J, Camacho M, Quer M, et al. Pretreatment count of peripheral neutrophils, monocytes, and lymphocytes as independent prognostic factor in patients with head and neck cancer. Head Neck. 2017;39(2):219–26. https://doi.org/10.1002/hed.24561.
Rosculet N, Zhou XC, Ha P, Tang M, Levine MA, Neuner G, et al. Neutrophil-to-lymphocyte ratio: prognostic indicator for head and neck squamous cell carcinoma. Head Neck. 2017;39(4):662–7. https://doi.org/10.1002/hed.24658.
Ponzetta A, Carriero R, Carnevale S, Barbagallo M, Molgora M, Perucchini C, et al. Neutrophils driving unconventional T cells mediate resistance against murine sarcomas and selected human tumors. Cell. 2019;178(2):346-360.e24. https://doi.org/10.1016/j.cell.2019.05.047.
Hedrick CC, Malanchi I. Neutrophils in cancer: heterogeneous and multifaceted. Nat Rev Immunol. 2022;22(3):173–87. https://doi.org/10.1038/s41577-021-00571-6.
Antonio N, Bønnelykke-Behrndtz ML, Ward LC, Collin J, Christensen IJ, Steiniche T, et al. The wound inflammatory response exacerbates growth of pre-neoplastic cells and progression to cancer. EMBO J. 2015;34(17):2219–36. https://doi.org/10.15252/embj.201490147.
Xu W, Dong J, Zheng Y, Zhou J, Yuan Y, Ta HM, et al. Immune-checkpoint protein VISTA regulates antitumor immunity by controlling myeloid cell-mediated inflammation and immunosuppression. Cancer Immunol Res. 2019;7(9):1497–510. https://doi.org/10.1158/2326-6066.CIR-18-0489.
Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L, et al. Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell. 2009;16(3):183–94. https://doi.org/10.1016/j.ccr.2009.06.017.
Spiegel A, Brooks MW, Houshyar S, Reinhardt F, Ardolino M, Fessler E, et al. Neutrophils suppress intraluminal NK cell-mediated tumor cell clearance and enhance extravasation of disseminated carcinoma cells. Cancer Discov. 2016;6(6):630–49. https://doi.org/10.1158/2159-8290.CD-15-1157.
Mishalian I, Bayuh R, Eruslanov E, Michaeli J, Levy L, Zolotarov L, et al. Neutrophils recruit regulatory T-cells into tumors via secretion of CCL17—a new mechanism of impaired antitumor immunity. Int J Cancer. 2014;135(5):1178–86. https://doi.org/10.1002/ijc.28770.
Tyagi A, Sharma S, Wu K, Wu SY, Xing F, Liu Y, et al. Nicotine promotes breast cancer metastasis by stimulating N2 neutrophils and generating pre-metastatic niche in lung. Nat Commun. 2021;12(1):474. https://doi.org/10.1038/s41467-020-20733-9.
Singhal S, Bhojnagarwala PS, O’Brien S, Moon EK, Garfall AL, Rao AS, Quatromoni JG, et al. Origin and role of a subset of tumor-associated neutrophils with antigen-presenting cell features in early-stage human lung cancer. Cancer Cell. 2016;30(1):120–35. https://doi.org/10.1016/j.ccell.2016.06.001.
Gershkovitz M, Caspi Y, Fainsod-Levi T, Katz B, Michaeli J, Khawaled S, et al. TRPM2 mediates neutrophil killing of disseminated tumor cells. Cancer Res. 2018;78(10):2680–90. https://doi.org/10.1158/0008-5472.CAN-17-3614.
Massara M, Bonavita O, Savino B, Caronni N, Mollica Poeta V, Sironi M, et al. ACKR2 in hematopoietic precursors as a checkpoint of neutrophil release and anti-metastatic activity. Nat Commun. 2018;9(1):676. https://doi.org/10.1038/s41467-018-03080-8.
Matlung HL, Babes L, Zhao XW, van Houdt M, Treffers LW, van Rees DJ, et al. Neutrophils kill antibody-opsonized cancer cells by trogoptosis. Cell Rep. 2018;23(13):3946-3959.e6. https://doi.org/10.1016/j.celrep.2018.05.082.
He M, Peng A, Huang XZ, Shi DC, Wang JC, Zhao Q, et al. Peritumoral stromal neutrophils are essential for c-Met-elicited metastasis in human hepatocellular carcinoma. Oncoimmunology. 2016;5(10): e1219828. https://doi.org/10.1080/2162402X.2016.1219828.
Demers M, Wagner DD. NETosis: a new factor in tumor progression and cancer-associated thrombosis. Semin Thromb Hemost. 2014;40(3):277–83. https://doi.org/10.1055/s-0034-1370765.
Sagiv JY, Michaeli J, Assi S, Mishalian I, Kisos H, et al. Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer. Cell Rep. 2015;10(4):562–73. https://doi.org/10.1016/j.celrep.2014.12.039.
Pylaeva E, Lang S, Jablonska J. The essential role of type I interferons in differentiation and activation of tumor-associated neutrophils. Front Immunol. 2016;7:629. https://doi.org/10.3389/fimmu.2016.00629.
Jaillon S, Ponzetta A, Di Mitri D, Santoni A, Bonecchi R, Mantovani A. Neutrophil diversity and plasticity in tumour progression and therapy. Nat Rev Cancer. 2020;20(9):485–503. https://doi.org/10.1038/s41568-020-0281-y.
Silvestre-Roig C, Fridlender ZG, Glogauer M, Scapini P. Neutrophil diversity in health and disease. Trends Immunol. 2019;40(7):565–83. https://doi.org/10.1016/j.it.2019.04.012.
Fridlender ZG, Albelda SM. Tumor-associated neutrophils: friend or foe? Carcinogenesis. 2012;33(5):949–55. https://doi.org/10.1093/carcin/bgs123.
Wu Y, Zhao Q, Peng C, Sun L, Li XF, Kuang DM. Neutrophils promote motility of cancer cells via a hyaluronan-mediated TLR4/PI3K activation loop. J Pathol. 2011;225(3):438–47. https://doi.org/10.1002/path.2947.
Geh D, Leslie J, Rumney R, Reeves HL, Bird TG, Mann DA. Neutrophils as potential therapeutic targets in hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2022;19(4):257–73. https://doi.org/10.1038/s41575-021-00568-5.
Redman JM, Friedman J, Robbins Y, Sievers C, Yang X, Lassoued W, et al. Enhanced neoepitope-specific immunity following neoadjuvant PD-L1 and TGF-β blockade in HPV-unrelated head and neck cancer. J Clin Invest. 2022;132(18): e161400. https://doi.org/10.1172/JCI161400.
Tyagi A, Wu SY, Sharma S, Wu K, Zhao D, Deshpande R, et al. Exosomal miR-4466 from nicotine-activated neutrophils promotes tumor cell stemness and metabolism in lung cancer metastasis. Oncogene. 2022;41(22):3079–92. https://doi.org/10.1038/s41388-022-02322-w.
Li Q, Chen W, Li Q, Mao J, Chen X. A novel neutrophil extracellular trap signature to predict prognosis and immunotherapy response in head and neck squamous cell carcinoma. Front Immunol. 2022;13:1019967. https://doi.org/10.3389/fimmu.2022.1019967.
Peng ZP, Jiang ZZ, Guo HF, Zhou MM, Huang YF, Ning WR, et al. Glycolytic activation of monocytes regulates the accumulation and function of neutrophils in human hepatocellular carcinoma. J Hepatol. 2020;73(4):906–17. https://doi.org/10.1016/j.jhep.2020.05.004.
Gulati S, Crist M, Riaz MK, Takiar V, Lehn M, Monroe I, et al. Durvalumab plus cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma: an open-label, non-randomized, phase-2 clinical trial. Clin Cancer Res. 2023. https://doi.org/10.1158/1078-0432.CCR-22-3886.
Damasio MPS, Nascimento CS, Andrade LM, de Oliveira VL, Calzavara-Silva CE. The role of T-cells in head and neck squamous cell carcinoma: From immunity to immunotherapy. Front Oncol. 2022;12:1021609. https://doi.org/10.3389/fonc.2022.1021609.
Wang S, Wu ZZ, Zhu SW, Wan SC, Zhang MJ, Zhang BX, et al. CTLA-4 blockade induces tumor pyroptosis via CD8+ T cells in head and neck squamous cell carcinoma. Mol Ther. 2023;S1525–0016(23):00121–31. https://doi.org/10.1016/j.ymthe.2023.02.023.
Knitz MW, Bickett TE, Darragh LB, Oweida AJ, Bhatia S, Van Court B, et al. Targeting resistance to radiation-immunotherapy in cold HNSCCs by modulating the Treg-dendritic cell axis. J Immunother Cancer. 2021;9(4): e001955. https://doi.org/10.1136/jitc-2020-001955.
Kusmartsev S, Nefedova Y, Yoder D, Gabrilovich DI. Antigen-specific inhibition of CD8+ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species. J Immunol. 2004;172(2):989–99. https://doi.org/10.4049/jimmunol.172.2.989.
Governa V, Trella E, Mele V, Tornillo L, Amicarella F, Cremonesi E, et al. The interplay between neutrophils and CD8+ T cells improves survival in human colorectal cancer. Clin Cancer Res. 2017;23(14):3847–58. https://doi.org/10.1158/1078-0432.CCR-16-2047.
Pietrobon V, Marincola FM. Hypoxia and the phenomenon of immune exclusion. J Transl Med. 2021;19(1):9. https://doi.org/10.1186/s12967-020-02667-4.
Teijeira Á, Garasa S, Gato M, Alfaro C, Migueliz I, Cirella A, et al. CXCR1 and CXCR2 chemokine receptor agonists produced by tumors induce neutrophil extracellular traps that interfere with immune cytotoxicity. Immunity. 2020;52(5):856-871.e8. https://doi.org/10.1016/j.immuni.2020.03.001.
Li K, Tandurella JA, Gai J, Zhu Q, Lim SJ, Thomas DL 2nd, et al. Multi-omic analyses of changes in the tumor microenvironment of pancreatic adenocarcinoma following neoadjuvant treatment with anti-PD-1 therapy. Cancer Cell. 2022;40(11):1374-1391.e7. https://doi.org/10.1016/j.ccell.2022.10.001.
Canè S, Barouni RM, Fabbi M, Cuozzo J, Fracasso G, Adamo A, et al. Neutralization of NET-associated human ARG1 enhances cancer immunotherapy. Sci Transl Med. 2023;15(687): eabq6221. https://doi.org/10.1126/scitranslmed.abq6221.