Cancer cell immune mimicry delineates onco-immunologic modulation

• Main Authors: Rui Gao, Bin He, Qitao Huang, Zifeng Wang, Min Yan, Eric Wing-Fai Lam, Suxia Lin, Bo Wang, Quentin Liu
• Format: Article
• Language: English
• Published: Elsevier 2021-10-01
• Series: iScience
• Subjects: Biological sciences; Immunology; Genomics
• Online Access: http://www.sciencedirect.com/science/article/pii/S2589004221011019

Summary: Immune transcripts are essential for depicting onco-immunologic interactions. However, whether cancer cells mimic immune transcripts to reprogram onco-immunologic interaction remains unclear. Here, single-cell transcriptomic analyses of 7,737 normal and 37,476 cancer cells reveal increased immune transcripts in cancer cells. Cells gradually acquire immune transcripts in malignant transformation. Notably, cancer cell-derived immune transcripts contribute to distinct prognoses of immune gene signatures. Optimized immune response signature (oIRS), obtained by excluding cancer-related immune genes from immune gene signatures, and offers a more reliable prognostic value. oIRS reveals that antigen presentation, NK cell killing and T cell signaling are associated with favorable prognosis. Patients with higher oIRS expression are associated with favorable responses to immunotherapy. Indeed, CD83+ cell infiltration, which indicates antigen presentation activity, predicts favorable prognosis in breast cancer. These findings unveil that immune mimicry is a distinct cancer hallmark, providing an example of cancer cell plasticity and a refined view of tumor microenvironment.