PMID- 36864443 OWN - NLM STAT- MEDLINE DCOM- 20230310 LR - 20230310 IS - 1479-5876 (Electronic) IS - 1479-5876 (Linking) VI - 21 IP - 1 DP - 2023 Mar 3 TI - CD206(+) tumor-associated macrophages interact with CD4(+) tumor-infiltrating lymphocytes and predict adverse patient outcome in human laryngeal squamous cell carcinoma. PG - 167 LID - 10.1186/s12967-023-03910-4 [doi] LID - 167 AB - BACKGROUND: Tumor-associated macrophages (TAMs) are major component in the tumor microenvironment (TME) and play regulatory role in tumor progression. We aimed to investigate the infiltration and prognostic value of TAMs in laryngeal squamous cell carcinoma (LSCC) and to reveal the underlying mechanism of TAM subgroups in tumorigenesis. METHODS: Hematoxylin and eosin (HE) staining were performed to define the tumor nest and stroma of LSCC tissue microarrays. CD206 + /CD163 + and iNOS + TAM infiltrating profiles were obtained and analyzed through double-labeling immunofluorescence and immunohistochemical staining. The recurrence-free (RFS) and overall survival (OS) curves based on the infiltration of TAMs were plotted using the Kaplan-Meier method. Infiltration of macrophages, T lymphocytes and their corresponding subgroups were analyzed in fresh LSCC tissue samples by flow cytometry. RESULTS: We found that CD206(+) rather than CD163(+) M2-like TAMs were the most enriched population in the TME of human LSCC. CD206(+) macrophages localized mostly in the tumor stroma (TS) rather than the tumor nest (TN) region. In contrast, relatively low infiltration of iNOS(+) M1-like TAMs were found in the TS and almost none in the TN region. High level of TS CD206(+) TAM infiltration correlated with poor prognosis. Interestingly, we identified a HLA-DR(high) CD206(+) macrophage subgroup that was significantly associated with the tumor-infiltrating CD4(+) T lymphocytes and showed different surface costimulatory molecule expression than that of the HLA-DR(low/)-CD206(+) subgroup. Taken together, our results indicate that HLA-DR(high)-CD206(+) is a highly activated subgroup of CD206 + TAMs that may interact with CD4 + T cells through MHC-II axis and promote tumorigenesis. CI - (c) 2023. The Author(s). FAU - Heng, Yu AU - Heng Y AD - ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, People's Republic of China. FAU - Zhu, Xiaoke AU - Zhu X AD - ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, People's Republic of China. FAU - Lin, Hanqing AU - Lin H AD - ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, People's Republic of China. FAU - Jingyu, Ma AU - Jingyu M AD - ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, People's Republic of China. FAU - Ding, Xuping AU - Ding X AD - Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China. FAU - Tao, Lei AU - Tao L AD - ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, People's Republic of China. lei.tao@fdeent.org. FAU - Lu, Liming AU - Lu L AD - Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China. youlanda2009@sjtu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230303 PL - England TA - J Transl Med JT - Journal of translational medicine JID - 101190741 RN - 0 (MRC1 protein, human) SB - IM MH - Humans MH - Carcinogenesis MH - CD4-Positive T-Lymphocytes MH - Cell Transformation, Neoplastic MH - *Head and Neck Neoplasms MH - Lymphocytes, Tumor-Infiltrating MH - Squamous Cell Carcinoma of Head and Neck MH - Tumor Microenvironment MH - *Tumor-Associated Macrophages PMC - PMC9983170 OTO - NOTNLM OT - CD4+ T cell interaction OT - Immunosuppressive microenvironment OT - Laryngeal squamous cell carcinoma OT - Macrophage infiltrating pattern OT - Prognosis OT - Tumor-associated macrophages COIS- There is no competing interests. EDAT- 2023/03/03 06:00 MHDA- 2023/03/07 06:00 PMCR- 2023/03/03 CRDT- 2023/03/02 23:34 PHST- 2022/02/09 00:00 [received] PHST- 2023/01/21 00:00 [accepted] PHST- 2023/03/02 23:34 [entrez] PHST- 2023/03/03 06:00 [pubmed] PHST- 2023/03/07 06:00 [medline] PHST- 2023/03/03 00:00 [pmc-release] AID - 10.1186/s12967-023-03910-4 [pii] AID - 3910 [pii] AID - 10.1186/s12967-023-03910-4 [doi] PST - epublish SO - J Transl Med. 2023 Mar 3;21(1):167. doi: 10.1186/s12967-023-03910-4.