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
Affiliations
Rui Gao
Department of Medical Oncology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 510275, P.R. China; 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
Bin He
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
Qitao Huang
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
Zifeng Wang
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
Min Yan
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
Eric Wing-Fai Lam
Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, W12 ONN, UK
Suxia Lin
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; Corresponding author
Bo Wang
Department of Medical Oncology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 510275, P.R. China; Corresponding author
Quentin Liu
Department of Medical Oncology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 510275, P.R. China; 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; Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, P.R. China; Corresponding author
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.
