Cancer cell immune mimicry delineates onco-immunologic modulation

Rui Gao; Bin He; Qitao Huang; Zifeng Wang; Min Yan; Eric Wing-Fai Lam; Suxia Lin; Bo Wang; Quentin Liu

doi:10.1016/j.isci.2021.103133

Cancer cell immune mimicry delineates onco-immunologic modulation

iScience. 2021 Sep 15;24(10):103133. doi: 10.1016/j.isci.2021.103133. eCollection 2021 Oct 22.

Authors

Rui Gao^{1

2}, Bin He², Qitao Huang², Zifeng Wang², Min Yan², Eric Wing-Fai Lam³, Suxia Lin², Bo Wang¹, Quentin Liu^{1

2

4}

Affiliations

¹ Department of Medical Oncology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 510275, P.R. China.
² State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.
³ Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, W12 ONN, UK.
⁴ Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, P.R. China.

Abstract

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.

Keywords: Biological sciences; Genomics; Immunology.