Pan-Cancer Analysis of Ligand-Receptor Cross-talk in the Tumor Microenvironment.

Cancer research 2021 Apr 01

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Signaling between cancer and nonmalignant (stromal) cells in the tumor microenvironment (TME) is a key to tumor progression. Here, we deconvoluted bulk tumor transcriptomes to infer cross-talk between ligands and receptors on cancer and stromal cells in the TME of 20 solid tumor types. This approach recovered known transcriptional hallmarks of cancer and stromal cells and was concordant with single-cell, in situ hybridization and IHC data. Inferred autocrine cancer cell interactions varied between tissues but often converged on Ephrin, BMP, and FGFR-signaling pathways. Analysis of immune checkpoints nominated interactions with high levels of cancer-to-immune cross-talk across distinct tumor types. Strikingly, PD-L1 was found to be highly expressed in stromal rather than cancer cells. Overall, our study presents a new resource for hypothesis generation and exploration of cross-talk in the TME. SIGNIFICANCE: This study provides deconvoluted bulk tumor transcriptomes across multiple cancer types to infer cross-talk in the tumor microenvironment. ©2021 American Association for Cancer Research.

Citation

Umesh Ghoshdastider, Neha Rohatgi, Marjan Mojtabavi Naeini, Probhonjon Baruah, Egor Revkov, Yu Amanda Guo, Simone Rizzetto, Angeline M L Wong, Sundar Solai, Tin T Nguyen, Joe Poh Sheng Yeong, Jabed Iqbal, Puay Hoon Tan, Balram Chowbay, Ramanuj Dasgupta, Anders J Skanderup. Pan-Cancer Analysis of Ligand-Receptor Cross-talk in the Tumor Microenvironment. Cancer research. 2021 Apr 01;81(7):1802-1812