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ORIGINAL RESEARCH article

Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
Volume 12 - 2024 | doi: 10.3389/fcell.2024.1466767
This article is part of the Research Topic Single Cell Landscapes in Gastrointestinal Cancer View all articles

Single-Cell Transcriptome Analysis Identifies a Novel Tumorassociated Macrophage Subtype Predicting Better Prognosis in Pancreatic Ductal Adenocarcinoma

Provisionally accepted
Wang Xiaonan Wang Xiaonan Dongyi Li Dongyi Li Bo Zhu Bo Zhu *Zi-Chun Hua Zi-Chun Hua *
  • China Pharmaceutical University, Nanjing, China

The final, formatted version of the article will be published soon.

    Background: Characterized by an immune-suppressive tumor microenvironment (TME), pancreatic ductal adenocarcinoma (PDAC) is well-known for its poor prognosis. Tumor associated macrophages (TAMs) play a critical role in PDAC TME. An in-depth understanding of TAMs is helpful to develop new strategies for immunotherapy.Methods: A large number of single-cell RNA sequencing data and bulk RNA sequencing data of PDAC were collected for systematic bioinformatics analysis. Characterize subtypes of TAMs at single-cell resolution. and its effect on prognosis. Differential gene analysis and cell-cell communication were used to describe the effect on prognosis and validated by the TCGA dataset.Results: We used two prognosis-favorable genes, SLC12A5 and ENPP2, to identify a benign M2-like TAMs (bM2-like TAMs), which shared similarities with C1QC+ TAMs, CXCL9+ TAMs and CD169+ TAMs, by analyzing scRNA-seq data and bulk RNA data of PDAC. The bM2-like TAMs were revealed to promote T cell activation and proliferation through ALCAM/CD6 interaction. Meanwhile, the bM2-like TAMs were responsible for stroma modeling by altering αSMA+ /αSMAcell ratio. On the contrast, the rest of the M2-like TAMs were defined as malignant M2-like TAMs (mM2-like TAMs), partly overlapping with SPP1+ TAMs. mM2-like TAMs were revealed to promote tumor progression by secretion of MIF and SPP1. Conclusion: Our study used two prognosis-favorable genes to divide M2-like TAMs of PDAC into anti-tumor bM2-like TAMs and pro-tumor mM2-like TAMs. The bM2-like TAMs activate T cells through ALCAM/CD6 and generate prognosis-favorable αSMA+ myofibroblasts through secreting TGFβ, which brings insight into heterogeneity of TAMs, prognosis prediction and immunotherapy of PDAC.

    Keywords: single-cell sequencing, Pancreatic Cancer, tumor associated macrophages, Tumor Microenvironment, prognosis

    Received: 18 Jul 2024; Accepted: 14 Oct 2024.

    Copyright: © 2024 Xiaonan, Li, Zhu and Hua. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Bo Zhu, China Pharmaceutical University, Nanjing, China
    Zi-Chun Hua, China Pharmaceutical University, Nanjing, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.