• Rongrong Wu, Masanori Oshi, Mariko Asaoka, Li Yan, BeneschMatthew G KMGKDepartment of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY., Thaer Khoury, Masayuki Nagahashi, Yasuo Miyoshi, Itaru Endo, Takashi Ishikawa, and Kazuaki Takabe.
• Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY.
• Ann. Surg. 2023 Oct 1; 278 (4): 587597587-597.

ObjectiveTo investigate the clinical relevance of intratumoral tumor infiltrating lymphocytes (TILs) in breast cancer as measured by computational deconvolution of bulk tumor transcriptomes.Summary Background DataCommonly assessed TILs, located in tumor stroma without direct contact with cancer cells (stromal TILs), correlate with breast cancer treatment response and survival. The clinical relevance of intratumoral TILs has been less studied partly due to their rarity; however, they may have nonnegligible effects given their direct contact with cancer cells.MethodsIn all, 5870 breast cancer patients from TCGA, METABRIC, GSE96058, GSE25066, GSE163882, GSE123845, and GSE20271 cohorts were analyzed and validated.ResultsThe intratumoral TIL score was established by the sum of all types of lymphocytes using the xCell algorithm. This score was the highest in triple-negative breast cancer (TNBC) and the lowest in the ER-positive/HER2-negative subtype. It correlated with cytolytic activity and infiltrations of dendritic cells, macrophages, and monocytes, and uniformly enriched immune-related gene sets regardless of subtype. Intratumoral TIL-high tumors correlated with higher mutation rates and significant cell proliferation on biological, pathological, and molecular analyses only in the ER-positive/HER2-negative subtype. It was significantly associated with pathological complete response after anthracycline- and taxane-based neoadjuvant chemotherapy in about half of the cohorts, regardless of the subtype. Intratumoral TIL-high tumors correlated with better overall survival in HER2-positive and TNBC subtypes consistently in 3 cohorts.ConclusionsIntratumoral TILs estimated by transcriptome computation were associated with increased immune response and cell proliferation in ER-positive/HER2-negative and better survival in HER2-positive and TNBC subtypes, but not always with pathological complete response after neoadjuvant chemotherapy.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.

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