Research Paper Advance Articles
Single-cell immune escape correlation analysis: unraveling the prognostic influence of intercellular communication in the tumor microenvironment of colorectal cancer
- 1 Department of Radiology, The First Affiliated Hospital of Hunan College of TCM (Hunan Province Directly Affiliated TCM Hospital), Lusong, Zhuzhou, Hunan 412000, P.R. China
- 2 Department of Oncology, The First Affiliated Hospital of Hunan College of TCM (Hunan Province Directly Affiliated TCM Hospital), Lusong, Zhuzhou, Hunan 412000, P.R. China
Received: September 26, 2023 Accepted: June 3, 2024 Published: June 29, 2024
https://doi.org/10.18632/aging.205978How to Cite
Copyright: © 2024 Gan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: The role of immune escape-related genes in the tumor microenvironment (TME) in CRC remains unclear but is known to be crucial for CRC development.
Methods: We analyzed single-cell RNA-seq data from 13 CRC tumor samples, comprising 66,050 cells, using NMF to identify immune escape-related genes. We predicted the prognosis and immune response of novel TME cell clusters using a public CRC cohort and immunotherapy cohort.
Results: CRC single-cell analysis revealed distinct cell types, including plasma cells, epithelial cells, T cells, NK cells, goblet cells, intestinal cells, B cells, macrophages, fibroblasts, endothelial cells, and mast cells. These cell types were further grouped into new clusters based on immune escape-related gene annotations. Immunohistochemistry (IHC) confirmed the high expression of TGF-β+, JAK1+, and Calretinin+ in CRC tissues, validating key bioinformatics findings on their potential relevance in CRC pathology. Pseudo-temporal trajectory analysis showed the differentiation trajectory of different immune escape-related subtype cell clusters. Cellular communication analysis revealed extensive interactions between endothelial cells and immune escape-related metabolizing TME cell-related subtypes. SCENIC analysis identified transcription factors upstream of TME cell clusters with varying immune responses. Moreover, TME cell clusters associated with immune escape processes exhibited enrichment in the expression of CAF subtypes, CD8-depleted, M1, and M2 macrophages. Bulk-seq analysis demonstrated the significant prognostic importance of immune escape-related TME cell clusters in CRC. Remarkably, the immunotherapy cohort showed a significant immune response, especially in patients treated with immune ICB, involving CAFs, T cells, and macrophages.
Conclusion: Our study is the first to reveal the role of immune escape in mediating intercellular communication within the CRC microenvironment, elucidating the anti-tumor mechanisms and immune prognostic responses of distinct cell cluster subtypes.
Abbreviations
CRC: colorectal cancer; TME: tumor microenvironment; NMF: non-negative matrix factorization; IHC: immunohistochemistry; CAF: cancer-associated fibroblast; ICB: immune checkpoint blockade; DEGs: differential gene expression analysis; TCGA: The Cancer Genome Atlas; ICGC: International Cancer Genome Consortium; UMI: unique molecular identifiers; TSS: transcription start sites; RSS: Regulon Specificity Score; OS: overall survival; TIDE: Tumor Immune Dysfunction and Exclusion.