YING-CHUN SHENYeh C.-P.YUNG-MING JENGCHIUN HSUCHIH-HUNG HSUZHONG-ZHE LINYU-YUN SHAOLI-CHUN LUTSUNG-HAO LIUCHIEN-HUNG CHENANN-LII CHENG2022-02-072022-02-0720212072-6694https://www.scopus.com/inward/record.uri?eid=2-s2.0-85116982486&doi=10.3390%2fcancers13205142&partnerID=40&md5=d2780c078bbbd742230ce5a08cba4269https://scholars.lib.ntu.edu.tw/handle/123456789/593828Purpose: Tumor-infiltrating tissue-resident memory CD8 T cells (CD8 TRM; CD103+ CD8+) are considered tumor-specific and may correlate better with the tumor response to immune checkpoint blockade (ICB). This study evaluated the association of tumor-infiltrating CD8 TRM and their subsets with the efficacy of immunotherapy in patients with advanced hepatocellular carcinoma (HCC). Experimental Design: Consecutive HCC patients who received ICB in prospective trials were analyzed. Formalin-fixed paraffin-embedded tumor sections were stained for DAPI, CD8, CD103, CD39, programmed cell death-1 (PD-1), and programmed cell death ligand 1 (PD-L1) using a multiplex immunohistochemical method. The densities of CD8 T cells, CD8 TRM, and CD39+ or PD-L1+ subsets of CD8 TRM were correlated with tumor response and overall survival (OS). Results: A total of 73 patients were identified, and 48 patients with adequate pretreatment tumor specimens and complete follow-up were analyzed. A median of 32.7% (range: 0–92.6%) of tumor-infiltrating CD8 T cells were TRM . In subset analyses, 66.6% ± 34.2%, 69.8% ± 33.4%, and 0% of CD8 TRM cells coexpressed CD39, PD-L1, and PD-1, respectively. The objective response rates for CD8 T cell-high, CD8 TRM-high, CD39+ CD8 TRM-high, and PD-L1+ CD8 TRM-high groups were 41.7%, 37.5%, 37.5%, and 29.2%, respectively. Patients with CD8 T cell-high, but not those with CD8 TRM-high, CD39+ CD8 TRM-high, or PD-L1+ CD8 TRM-high, tumors, had significantly prolonged OS (p = 0.0429). Conclusions: Compared with total tumor-infiltrating CD8 T cells, tumor-infiltrating CD8 TRM or their subsets failed to provide additional advantages in predicting the efficacy of immunotherapy for HCC. ? 2021 by the authors. Licensee MDPI, Basel, Switzerland.[SDGs]SDG3CD8 antigen; immune checkpoint inhibitor; adult; aged; Article; cancer immunotherapy; cancer prognosis; CD8+ T lymphocyte; clinical article; drug efficacy; female; human; human cell; liver cell carcinoma; male; memory T lymphocyte; overall survival; predictive value; tumor associated leukocytejournal article10.3390/cancers132051422-s2.0-85116982486