title: Increased CD4 and CD8-positive T cell infiltrate signifies good prognosis in a subset of triple-negative breast cancer.
abstract: Tumour-infiltrating lymphocytes (TILs) signify immune response to tumour in a variety of cancers including breast cancer. However, earlier studies examining the clinical significance of TILs in breast cancers have generated mixed results. There are only a few that address the relationship between TILs and clinical outcomes in triple-negative breast cancers (TNBC). The aim of this study is to evaluate the clinical significance of TILs that express CD4 + and CD8 + , in TNBC. Immunohistochemical staining of CD4 and CD8 was performed on tissue microarrays of 164 cases of TNBC. TILs were counted separately as intratumoral when within the cancer cell nests (iTILs) and as stromal when within cancer stroma (sTILs). High CD8 + iTILs and sTILs, and CD4 + iTILs correlated with histologic grade. On Kaplan-Meier analysis, a significantly better survival rate was observed in high CD8 + iTIL (disease-free survival, DFS: P = 0.004, overall survival, OS: P = 0.02) and both high CD4 + iTILs (DFS: P = 0.025, OS: P = 0.023) and sTILs (DFS: P = 0.01, OS: P = 0.002). In multivariate analysis, CD8 + iTILs (DFS: P = 0.0095), CD4 + sTILs (DFS: P = 0.0084; OS: P = 0.0118), and CD4 (high) CD8 (high) CD8 iTILs (DFS: P = 0.0121; OS: P = 0.0329) and sTILs (DFS: P = 0.0295) showed significantly better survival outcomes. These results suggest that high levels of both CD8 + iTILs and CD4 + sTILs as well as CD4 (high) CD8 (high) iTILs and sTILs are independent prognostic factors in TNBC.
authors.affiliation: Department of Pathology, Ryukyu University Hospital, Okinawa, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: Department of Pathology, Singapore General Hospital, 20 College Road, Academia, Level 10, Singapore, 169856, Singapore.
authors.forename: Aye Aye
authors.initials: AA
authors.lastname: Thike
authors.affiliation: Division of Research, Singapore General Hospital, Singapore, Singapore.
authors.forename: Huihua
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pathology, Singapore General Hospital, 20 College Road, Academia, Level 10, Singapore, 169856, Singapore.|Singapore Immunology Network, Agency of Science, Technology and Research, Singapore, Singapore.
authors.forename: Joe
authors.initials: J
authors.lastname: Yeong
authors.affiliation: Department of Medical Oncology, National Cancer Centre, Singapore, Singapore.
authors.forename: Si-Lin
authors.initials: SL
authors.lastname: Koo
authors.affiliation: Department of Medical Oncology, National Cancer Centre, Singapore, Singapore.
authors.forename: Rebecca Alexandra
authors.initials: RA
authors.lastname: Dent
authors.affiliation: Department of Pathology, Singapore General Hospital, 20 College Road, Academia, Level 10, Singapore, 169856, Singapore.
authors.forename: Puay Hoon
authors.initials: PH
authors.lastname: Tan
authors.affiliation: Department of Pathology, Singapore General Hospital, 20 College Road, Academia, Level 10, Singapore, 169856, Singapore. jabed.iqbal@sgh.com.sg.
authors.forename: Jabed
authors.initials: J
authors.lastname: Iqbal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology*; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D046888:Tissue Array Analysis; D064726:Triple Negative Breast Neoplasms / Q000276:immunology / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor
keywords: CD4; CD8; Lymphocytes; Overall survival; Triple-negative breast cancer (TNBC)