PMID- 33220295 OWN - NLM STAT- MEDLINE DCOM- 20210225 LR - 20211204 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 267 DP - 2021 Feb 15 TI - Tumor-regulated macrophage type 2 differentiation promotes immunosuppression in laryngeal squamous cell carcinoma. PG - 118798 LID - S0024-3205(20)31551-4 [pii] LID - 10.1016/j.lfs.2020.118798 [doi] AB - AIMS: Tumor-associated macrophage (TAM) residing in tumor microenvironment as the major niche cell made remarkable contribution to tumor growth. However, the functional role of macrophage and its different differentiating state as well as the regulating mechanism in laryngeal squamous cell carcinoma (LSCC) remains not fully clear. MATERIALS AND METHODS: LSCC samples were collected from patients. Human peripheral blood mononuclear cells (PBMC) were collected from volunteers' blood, and used for macrophage induction. Enzyme-Linked Immunosorbent Assay (ELISA) was performed to detect proinflammatory cytokines. Immunostaining was prepared to observe tumor tissues. KEY FINDINGS: Here, we found the number of type 2 macrophage (MPhi2) and PDL-1 expression was increased in LSCC that was correlated with poor prognosis in patients with LSCC. Tumor cells induced macrophage into type 2 differentiation by TGF-beta/Smad3 signaling. The primed MPhi2 produced IL-10 by activating JAK/STAT signaling that promoted PDL-1 expression in tumor cells leading to its immunosuppression. Inhibition of JAK/STAT signaling promoted tumor cells death from immune cells killing by regulating PDL-1 expression. Targeting cytokines TGF-beta or IL-10 synergistically enhances the sensitivity of tumors to chemotherapy in vivo. SIGNIFICANCE: In conclusion, our findings showed tumor cells and MPhi2 were bilaterally regulated through cytokines production that integrally advanced tumor progression through boosting anti-tumor immunity. It provides insight to develop immune strategies synergy with chemotherapy in treating laryngeal squamous cell carcinoma. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Zhang, Peng AU - Zhang P AD - Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. Electronic address: fcczhangp1@zzu.edu.cn. FAU - Zhang, Yanfei AU - Zhang Y AD - Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. FAU - Wang, Liang AU - Wang L AD - Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. FAU - Lou, Weihua AU - Lou W AD - Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. LA - eng PT - Journal Article DEP - 20201118 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (B7-H1 Antigen) RN - 0 (CD274 protein, human) RN - 0 (Cytokines) RN - 0 (STAT Transcription Factors) RN - EC 2.7.10.2 (Janus Kinases) SB - IM MH - B7-H1 Antigen/metabolism MH - Carcinoma, Squamous Cell/pathology MH - Cell Differentiation/immunology/physiology MH - Cell Proliferation MH - Cytokines/immunology/metabolism MH - Female MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Immunosuppression Therapy MH - Janus Kinases/metabolism MH - Laryngeal Neoplasms/metabolism MH - Leukocytes, Mononuclear/metabolism MH - Macrophages/*immunology/metabolism MH - Male MH - STAT Transcription Factors/metabolism MH - Signal Transduction/physiology MH - Squamous Cell Carcinoma of Head and Neck/*immunology/metabolism MH - Tumor Microenvironment/immunology MH - Tumor-Associated Macrophages/immunology/*metabolism/physiology OTO - NOTNLM OT - Immunosuppression OT - JAK/STAT signaling OT - Laryngeal squamous cell carcinoma OT - PDL-1 OT - Tumor-associated macrophage type 2 EDAT- 2020/11/22 06:00 MHDA- 2021/02/26 06:00 CRDT- 2020/11/21 20:07 PHST- 2020/08/31 00:00 [received] PHST- 2020/11/04 00:00 [revised] PHST- 2020/11/16 00:00 [accepted] PHST- 2020/11/22 06:00 [pubmed] PHST- 2021/02/26 06:00 [medline] PHST- 2020/11/21 20:07 [entrez] AID - S0024-3205(20)31551-4 [pii] AID - 10.1016/j.lfs.2020.118798 [doi] PST - ppublish SO - Life Sci. 2021 Feb 15;267:118798. doi: 10.1016/j.lfs.2020.118798. Epub 2020 Nov 18.