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A Single-Cell Atlas of Tumor-Infiltrating Immune Cells in Pancreatic Ductal Adenocarcinoma |
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| Authors: | Hao Wang Lu Chen Lisha Qi Na Jiang Zhibin Zhang Hua Guo Tianqiang Song Jun Li Hongle Li Ning Zhang Ruibing Chen |
| Institution: | 1. School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China;2. Department of Clinical Laboratory, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China;3. Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin, China;4. Department of General Surgery, Tianjin First Central Hospital, Tianjin, China;5. Department of Molecular Pathology, Clinical Pathology Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China;6. Peking University First Hospital, Peking University Health Science Center, Beijing, China |
| Abstract: | Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with limited treatment options. To guide the design of more effective immunotherapy strategies, mass cytometry was employed to characterize the cellular composition of the PDAC-infiltrating immune cells. The expression of 33 protein markers was examined at the single-cell level in more than two million immune cells from four types of clinical samples, including PDAC tumors, normal pancreatic tissues, chronic pancreatitis tissues, and peripheral blood. Based on the analyses, we identified 23 distinct T-cell phenotypes, with some cell clusters exhibiting aberrant frequencies in the tumors. Programmed cell death protein 1 (PD-1) was extensively expressed in CD4+ and CD8+ T cells and coexpressed with both stimulatory and inhibitory immune markers. In addition, we observed elevated levels of functional markers, such as CD137L and CD69, in PDAC-infiltrating immune cells. Moreover, the combination of PD-1 and CD8 was used to stratify PDAC tumors from The Cancer Genome Atlas database into three immune subtypes, with S1 (PD-1+CD8+) exhibiting the best prognosis. Further analysis suggested distinct molecular mechanisms for immune exclusion in different subtypes. Taken together, the single-cell protein expression data depicted a detailed cell atlas of the PDAC-infiltrating immune cells and revealed clinically relevant information regarding useful cell phenotypes and targets for immunotherapy development. |
| Keywords: | cancer immunology mass cytometry pancreatic ductal adenocarcinoma single-cell analysis tumor microenvironment Ab"} {"#name":"keyword" "$":{"id":"kwrd0040"} "$$":[{"#name":"text" "_":"antibody CCR5"} {"#name":"keyword" "$":{"id":"kwrd0050"} "$$":[{"#name":"text" "_":"CC chemokine receptor 5 CP"} {"#name":"keyword" "$":{"id":"kwrd0060"} "$$":[{"#name":"text" "_":"chronic pancreatitis CTLA-4"} {"#name":"keyword" "$":{"id":"kwrd0070"} "$$":[{"#name":"text" "_":"cytotoxic T lymphocyte–associated protein 4 ECM"} {"#name":"keyword" "$":{"id":"kwrd0080"} "$$":[{"#name":"text" "_":"extracellular matrix EM"} {"#name":"keyword" "$":{"id":"kwrd0090"} "$$":[{"#name":"text" "_":"effector memory FoxP3"} {"#name":"keyword" "$":{"id":"kwrd0100"} "$$":[{"#name":"text" "_":"forkhead box P3 GSVA"} {"#name":"keyword" "$":{"id":"kwrd0110"} "$$":[{"#name":"text" "_":"gene set variation analysis ICOS"} {"#name":"keyword" "$":{"id":"kwrd0120"} "$$":[{"#name":"text" "_":"inducible T-cell costimulatory IHC"} {"#name":"keyword" "$":{"id":"kwrd0130"} "$$":[{"#name":"text" "_":"immunohistochemistry LAG-3"} {"#name":"keyword" "$":{"id":"kwrd0140"} "$$":[{"#name":"text" "_":"lymphocyte-activation gene 3 MP"} {"#name":"keyword" "$":{"id":"kwrd0150"} "$$":[{"#name":"text" "_":"mononuclear phagocyte Nadj"} {"#name":"keyword" "$":{"id":"kwrd0160"} "$$":[{"#name":"text" "_":"normal adjacent OX40"} {"#name":"keyword" "$":{"id":"kwrd0170"} "$$":[{"#name":"text" "_":"tumor necrosis factor receptor superfamily member 4 PBMC"} {"#name":"keyword" "$":{"id":"kwrd0180"} "$$":[{"#name":"text" "_":"peripheral blood mononuclear cell PD-1"} {"#name":"keyword" "$":{"id":"kwrd0190"} "$$":[{"#name":"text" "_":"programmed cell death protein 1 PDAC"} {"#name":"keyword" "$":{"id":"kwrd0200"} "$$":[{"#name":"text" "_":"pancreatic ductal adenocarcinoma TCGA"} {"#name":"keyword" "$":{"id":"kwrd0210"} "$$":[{"#name":"text" "_":"The Cancer Genome Atlas TIM-3"} {"#name":"keyword" "$":{"id":"kwrd0220"} "$$":[{"#name":"text" "_":"T-cell immunoglobulin and mucin-domain containing-3 Tm"} {"#name":"keyword" "$":{"id":"kwrd0230"} "$$":[{"#name":"text" "_":"tumor margin TME"} {"#name":"keyword" "$":{"id":"kwrd0240"} "$$":[{"#name":"text" "_":"tumor microenvironment Tn"} {"#name":"keyword" "$":{"id":"kwrd0250"} "$$":[{"#name":"text" "_":"tumor nest Treg"} {"#name":"keyword" "$":{"id":"kwrd0260"} "$$":[{"#name":"text" "_":"regulatory T cell tSNE"} {"#name":"keyword" "$":{"id":"kwrd0270"} "$$":[{"#name":"text" "_":"t-distributed stochastic neighbor embedding |
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