Heterogeneity of exhausted T cells in the tumor microenvironment is linked to patient survival following resection in hepatocellular carcinoma. (1st January 2020)

• Record Type: Journal Article
• Authors: Liu, Fangming; Liu, Weiren; Sanin, David E.; Jia, Guangshuai; Tian, Mengxin; Wang, Han; Zhu, Bijun; Lu, Yan; Qiao, Tiankui; Wang, Xiangdong; Shi, Yinghong; Wu, Duojiao
• Is Part Of: Oncoimmunology. Volume 9:Number 1(2020)
• Publication Date: 2020-01-01
• Subjects: T cell exhaustion -- hepatocellular carcinoma -- prognosis -- microenvironment; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2020.1746573
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: Despite the success of monotherapies based on blockade of programmed cell death 1 (PD-1) in human melanoma, most patients do not experience durable clinical benefit. T-cell infiltration and/or the presence of PD-L1 in tumors may be used as indicators of clinical response; However, recent studies reported that preexisting tumor-specific T cells may have limited reinvigoration capacity. Therefore, evaluating status of T cells of tumor-adjacent area and its impact on the prognosis are very important. Here, we examined 117 surgical samples from HCC patients for infiltration of exhausted T cell (Tex) including CD4 + -Tex, CD8 + -Tex and regulatory T cell (FOXP3 + -Treg) in tumor and adjacent tissue. CD3 + CD45RO + T cells were sorted from adjacent area or tumor core, then the clusters and heterogeneity of T cells were further interrogated by single-cell RNA sequencing. As a result, we suggested that abundance or location of T cell subsets is differentially correlate with long-term clinical outcome of HCC. In contrast with CD4 + T or CD4 + -Tex, the infiltration of CD8 + T or CD8 + -Tex cells was closely linked to overall or recurrence-free survival. FOXP3 + -Treg is more predictive of early recurrence. Single-cell transcriptional analysis demonstrates the composition of CD4 + -Tex, CD8 + -Tex, and FOXP3 + -Treg is shifted in tumor and adjacent tissue. Molecular profiles including genes coding checkpoint receptors, effector molecules are distinct between CD4 + -Tex, CD8 + -Tex, though some common features of CD4 + and CD8 + T cell exhaustion are revealed. In conclusion, we underline the heterogeneity and clinical relevance of Tex cells in HCC patients. A better understanding of Tex is critical for HCC monitoring and treatment.