Based on Immune Microenvironment and Genomic Status, Exploring Immunotherapy in Advanced Hidradenocarcinoma: A Retrospective Analysis
DOI:
https://doi.org/10.2340/actadv.v104.22146Keywords:
hidradenocarcinoma, NGS, PD-1 inhibitor, immunotherapy, immune microenvironmentAbstract
There are no standard treatment guidelines for hidradenocarcinoma, and the immune microenvironment and genomic data are very limited. Thus, in this study the immune microenvironment and genomic indicators in hidradenocarcinoma was investigated, and immunotherapy for hidradenocarcinoma was initially explored. Forty-seven hidradenocarcinoma patients were retrospectively collected. Immunohistochemical staining was performed to identify CD3/CD8+ T cells and programmed death ligand-1 expression. In total, 89.4% and 10.6% of samples had Immunoscores of 0–25% and 25–70%. Tumour proportion score distribution was as follows: tumour proportion score < 1% in 72.4%, 1–5% in 17.0%, and > 5% in 10.6%. Combined positive score distribution was as follows: combined positive score < 1 in 63.8%, 1–5 in 14.9%, and > 5 in 21.3%. Next-generation sequencing revealed that TP53 (33%), PI3KCA (22%), and ERBB3 (22%) were the most frequently mutated genes. The PI3K-Akt signalling pathway, growth, and MAPK signalling pathways were significantly enriched. Five patients had a low TMB (< 10 muts/Mb), and 9 patients had MSS. Three patients treated with immune combined with chemotherapy achieved significant tumour regression, and the progression-free survival was 28.8 months. In conclusion, the hidradenocarcinoma immune microenvironment tends to be noninflammatory. Evidence-based targets for targeted therapy are lacking. Immunotherapy combined with chemotherapy may be better for most advanced hidradenocarcinoma patients with a noninflammatory microenvironment.
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Gibbs DC, Yeung H, Blalock TW. Incidence and trends of cutaneous adnexal tumors in the United States in 2000-2018: a population-based study. J Am Acad Dermatol 2023; 88: 226-228.
https://doi.org/10.1016/j.jaad.2022.04.052 DOI: https://doi.org/10.1016/j.jaad.2022.04.052
Guillot B. Unusual cutaneous malignancies: cutaneous adnexal tumours. In: Belkacémi Y, Mirimanoff R-O, Ozsahin M, editors. Management of rare adult tumours. Paris: Springer; 2009: p. 471-477.
https://doi.org/10.1007/978-2-287-92246-6_53 DOI: https://doi.org/10.1007/978-2-287-92246-6_53
Baker MS, Yin VT, Ivan D, Allen RC, Carter KD, Esmaeli B, et al. Epidemiology and prognosis of primary periocular sweat gland carcinomas. Ophthalmic Plast Reconstr Surg 2017; 33: 101-105.
https://doi.org/10.1097/IOP.0000000000000658 DOI: https://doi.org/10.1097/IOP.0000000000000658
Amel T, Olfa G, Faten H, Makrem H, Slim BA, Moncef M. Metastatic hidradenocarcinoma: surgery and chemotherapy. N Am J Med Sci 2009; 1: 372-374.
Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science (New York, NY) 2011; 331: 1565-1570.
https://doi.org/10.1126/science.1203486 DOI: https://doi.org/10.1126/science.1203486
In GK, Nallagangula A, Choi JS, Tachiki L, Blackburn MJ, Capone S, et al. Clinical activity of PD-1 inhibition in the treatment of locally advanced or metastatic basal cell carcinoma. J Immunother Cancer 2022; 10(5): e004839.
https://doi.org/10.1136/jitc-2022-004839 DOI: https://doi.org/10.1136/jitc-2022-004839
Liu D, Schilling B, Liu D, Sucker A, Livingstone E, Jerby-Arnon L, et al. Integrative molecular and clinical modeling of clinical outcomes to PD1 blockade in patients with metastatic melanoma. Nat Med 2019; 25: 1916-1927.
https://doi.org/10.1038/s41591-019-0654-5 DOI: https://doi.org/10.1038/s41591-019-0654-5
Marabelle A, Fakih M, Lopez J, Shah M, Shapira-Frommer R, Nakagawa K, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol 2020; 21: 1353-1365.
https://doi.org/10.1016/S1470-2045(20)30445-9 DOI: https://doi.org/10.1016/S1470-2045(20)30445-9
O'Malley DM, Bariani GM, Cassier PA, Marabelle A, Hansen AR, De Jesus Acosta A, et al. Pembrolizumab in patients with microsatellite instability-high advanced endometrial cancer: results from the KEYNOTE-158 Study. J Clin Oncol 2022; 40: 752-761.
https://doi.org/10.1200/JCO.21.01874 DOI: https://doi.org/10.1200/JCO.21.01874
Pages F, Mlecnik B, Marliot F, Bindea G, Ou FS, Bifulco C, et al. International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study. Lancet 2018; 391: 2128-2139.
https://doi.org/10.1016/S0140-6736(18)30789-X DOI: https://doi.org/10.1016/S0140-6736(18)30789-X
Li C, Huang C, Mok TS, Zhuang W, Xu H, Miao Q, et al. Comparison of 22C3 PD-L1 expression between surgically resected specimens and paired tissue microarrays in non-small cell lung cancer. J Thorac Oncol 2017; 12: 1536-1543.
https://doi.org/10.1016/j.jtho.2017.07.015 DOI: https://doi.org/10.1016/j.jtho.2017.07.015
Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, et al. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet 2021; 398: 759-771.
https://doi.org/10.1016/S0140-6736(21)01234-4 DOI: https://doi.org/10.1016/S0140-6736(21)01234-4
Alwers E, Kather JN, Kloor M, Brobeil A, Tagscherer KE, Roth W, et al. Validation of the prognostic value of CD3 and CD8 cell densities analogous to the Immunoscore (R) by stage and location of colorectal cancer: an independent patient cohort study. J Pathol Clin Res 2023; 9: 129-136.
https://doi.org/10.1002/cjp2.304 DOI: https://doi.org/10.1002/cjp2.304
St Paul M, Ohashi PS. The roles of CD8 (+) T cell subsets in antitumor immunity. Trends Cell Biol 2020; 30: 695-704.
https://doi.org/10.1016/j.tcb.2020.06.003 DOI: https://doi.org/10.1016/j.tcb.2020.06.003
Kumagai S, Togashi Y, Kamada T, Sugiyama E, Nishinakamura H, Takeuchi Y, et al. The PD-1 expression balance between effector and regulatory T cells predicts the clinical efficacy of PD-1 blockade therapies. Nat Immunol 2020; 21: 1346-1358.
https://doi.org/10.1038/s41590-020-0769-3 DOI: https://doi.org/10.1038/s41590-020-0769-3
Jiang X, Wang J, Deng X, Xiong F, Ge J, Xiang B, et al. Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape. Mol Cancer 2019; 18: 10.
https://doi.org/10.1186/s12943-018-0928-4 DOI: https://doi.org/10.1186/s12943-018-0928-4
Fumet JD, Truntzer C, Yarchoan M, Ghiringhelli F. Tumour mutational burden as a biomarker for immunotherapy: current data and emerging concepts. Eur J Cancer 2020; 131: 40-50.
https://doi.org/10.1016/j.ejca.2020.02.038 DOI: https://doi.org/10.1016/j.ejca.2020.02.038
Yarchoan M, Hopkins A, Jaffee EM. Tumor mutational burden and response rate to PD-1 inhibition. N Engl J Med 2017; 377: 2500-2501.
https://doi.org/10.1056/NEJMc1713444 DOI: https://doi.org/10.1056/NEJMc1713444
Obermann H, Schmidle P, Steimle-Grauer SA, Pfarr N, Posch C. Exceptional response to anti-PD-1 treatment in a patient with metastatic cutaneous hidradenocarcinoma. Eur J Cancer 2021; 145: 143-145.
https://doi.org/10.1016/j.ejca.2020.12.015 DOI: https://doi.org/10.1016/j.ejca.2020.12.015
Zhang W, Yang X, Wang Y, He L, Cheng D. Anti-PD-1 immunotherapy for advanced small sweat gland neoplasm: a case report. Chin J Cancer Prev Treatment 2021; 28:703-707.
Spigel DR, Faivre-Finn C, Gray JE, Vicente D, Planchard D, Paz-Ares L, et al. Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. J Clin Oncol 2022; 40: 1301-1311.
https://doi.org/10.1200/JCO.21.01308 DOI: https://doi.org/10.1200/JCO.21.01308
Harms PW, Hovelson DH, Cani AK, Omata K, Haller MJ, Wang ML, et al. Porocarcinomas harbor recurrent HRAS-activating mutations and tumor suppressor inactivating mutations. Hum Pathol 2016; 51: 25-31.
https://doi.org/10.1016/j.humpath.2015.12.015 DOI: https://doi.org/10.1016/j.humpath.2015.12.015
Bosic M, Kirchner M, Brasanac D, Leichsenring J, Lier A, Volckmar AL, et al. Targeted molecular profiling reveals genetic heterogeneity of poromas and porocarcinomas. Pathology 2018; 50: 327-332.
https://doi.org/10.1016/j.pathol.2017.10.011 DOI: https://doi.org/10.1016/j.pathol.2017.10.011
Dias-Santagata D, Lam Q, Bergethon K, Baker GM, Iafrate AJ, Rakheja D, et al. A potential role for targeted therapy in a subset of metastasizing adnexal carcinomas. Mod Pathol 2011; 24: 974-982.
https://doi.org/10.1038/modpathol.2011.48 DOI: https://doi.org/10.1038/modpathol.2011.48
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