Academic Journal
Implication of IL6-positive Cancer-associated Fibroblasts in Merkel Cell Carcinoma Pathogenesis: A Possible Modulator of Immune Microenvironment
| Title: | Implication of IL6-positive Cancer-associated Fibroblasts in Merkel Cell Carcinoma Pathogenesis: A Possible Modulator of Immune Microenvironment |
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| Authors: | Zhenlong, Zheng, Dae San, Yoo, Shanshan, Li, Meiling, Pei, Sang Gyun, Lee, Ji Young, Kim, Kee Yang, Chung, Mi Ryung, Roh |
| Contributors: | Zhenlong Zheng, Dae San Yoo, Shanshan Li, Meiling Pei, Sang Gyun Lee, Ji Young Kim, Kee Yang Chung, Mi Ryung Roh, Roh, Mi Ryung |
| Source: | Anticancer Research. 42:4359-4369 |
| Publisher Information: | International Institute of Anticancer Research, 2022. |
| Publication Year: | 2022 |
| Subject Terms: | Skin Neoplasms, Interleukin-6, Carcinoma, Merkel Cell* / pathology, Cancer-Associated Fibroblasts* / pathology, CD8-Positive T-Lymphocytes, Prognosis, 3. Good health, Carcinoma, Merkel Cell, 03 medical and health sciences, Merkel cell carcinoma, Lymphocytes, Tumor-Infiltrating, 0302 clinical medicine, Cancer-Associated Fibroblasts, tumor infiltrating lymphocytes, Skin Neoplasms* / pathology, Tumor Microenvironment, Humans, Lymphocytes, Tumor-Infiltrating, cancer-associated fibroblasts |
| Description: | The role of cancer-associated fibroblasts (CAFs) in the pathogenesis of Merkel cell carcinoma (MCC) remains unknown. This study aimed to investigate the clinicopathological significance of CAF subpopulations and their association with tumor-infiltrating lymphocytes (TILs) in patients with MCC.Clinicopathological features and the status of microenvironment fibrosis (MF) around tumor masses were evaluated in 20 MCC patient and tissue sections. Alpha-smooth muscle actin (α-SMA)-positive CAFs (α-SMA+CAFs), interleukin-6-positive CAFs (IL6+CAFs), CD4-positive TILs (CD4+TILs), and CD8-positive TILs (CD8+TILs) in MCC tissue samples were investigated using immunohistochemistry.In a total of 20 MCC patients, high-MF was detected in 12 (60%) patients which was significantly associated with worse progression-free survival (p=0.048), but not with overall survival. CD4+/CD8+ TILs were frequently detected in MCC tissues. High-intra-tumoral CD8+TIL was significantly associated with better overall and progression-free survival (p=0.04 and p=0.015) in our cohort. High-αSMA+ CAFs were detected in 11 (55.0%) patients and high-IL6+CAFs in 10 (50.0%) patients. A negative association was found between high-IL6+CAF and high-intra-tumoral CD8+TILs (p=0.005). Patients with high IL6+CAFs showed worse overall/progression-free survival than patients with low-IL6+CAFs (p=0.022 and p=0.035).IL6+CAFs may largely influence the tumor immune microenvironment of MCC by modulating distinct T-cell populations and functions. This study provides a possible therapeutic target to overcome resistance to immune therapies in MCC. |
| Document Type: | Article |
| Language: | English |
| ISSN: | 1791-7530 0250-7005 |
| DOI: | 10.21873/anticanres.15936 |
| Access URL: | https://pubmed.ncbi.nlm.nih.gov/36039447 |
| Rights: | CC BY NC ND |
| Accession Number: | edsair.doi.dedup.....dec03c9a04c63c5679375b8020b82e4b |
| Database: | OpenAIRE |
| ISSN: | 17917530 02507005 |
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| DOI: | 10.21873/anticanres.15936 |