title: Comparison of tumor-infiltrating lymphocytes between primary and metastatic tumors in breast cancer patients.
abstract: The presence of tumor-infiltrating lymphocytes (TILs) is associated with favorable long-term outcome in breast cancer. However, little is known about changes in TILs during metastatic progression. To confirm our hypothesis that malignant tumors escape from the host immune system during metastasis, we evaluated the percentage of TILs in paired samples of primary and metastatic breast tumors. We retrospectively identified 25 patients with human epidermal growth factor receptor-2 (HER2+, n = 14) and triple negative (TN, n = 11) early breast cancer diagnosed between 1990 and 2009 at Tokai University Hospital (Isehara, Japan) and who subsequently experienced regional or distant recurrence confirmed by tumor biopsy/resection. Hematoxylin-eosin-stained slides of these paired samples were evaluated for stromal TILs. Immunohistochemical staining was carried out using primary antibodies against CD4, CD8, Foxp3, programmed cell death ligand 1 (PD-L1), PD-L2, and HLA class I for characterizing the TILs and breast tumors. The percentage of TILs in the primary tumors was significantly higher (average 34.6%) than that in metastatic tumors (average 15.7%) (paired t-test, P = 0.004) and that of CD8+and CD4+T cells significantly decreased from primary to metastatic tumors (paired t-test, P = 0.008 and P = 0.026, respectively). The PD-L1, PD-L2, and HLA class I antibody expression changed from positive to negative and vice versa from the primary to the metastatic tumors. Tumors at first metastatic recurrence in HER2+and TN breast cancers have a lower percentage of TILs and CD8+and CD4+T cells compared to primary tumors, which indicates that immune escape plays a role in tumor progression.
authors.affiliation: Department of Breast and Endocrine Surgery, School of Medicine, Tokai University, Isehara, Japan.
authors.forename: Rin
authors.initials: R
authors.lastname: Ogiya
authors.affiliation: Department of Breast and Endocrine Surgery, School of Medicine, Tokai University, Isehara, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Niikura
authors.affiliation: Department of Pathology, School of Medicine, Tokai University, Isehara, Japan.
authors.forename: Nobue
authors.initials: N
authors.lastname: Kumaki
authors.affiliation: Department of Medical Oncology, Ospedale San Raffaele, Milan, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Bianchini
authors.affiliation: Department of Experimental Therapeutics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Kitano
authors.affiliation: Department of Breast and Endocrine Surgery, Okayama University Hospital, Okayama, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Iwamoto
authors.affiliation: Department of Breast Surgical Oncology, St. Luke's International Hospital, Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hayashi
authors.affiliation: Department of Breast and Endocrine Surgery, School of Medicine, Tokai University, Isehara, Japan.
authors.forename: Kozue
authors.initials: K
authors.lastname: Yokoyama
authors.affiliation: Department of Breast and Endocrine Surgery, School of Medicine, Tokai University, Isehara, Japan.
authors.forename: Risa
authors.initials: R
authors.lastname: Oshitanai
authors.affiliation: Department of Breast and Endocrine Surgery, School of Medicine, Tokai University, Isehara, Japan.
authors.forename: Mayako
authors.initials: M
authors.lastname: Terao
authors.affiliation: Department of Breast and Endocrine Surgery, School of Medicine, Tokai University, Isehara, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Morioka
authors.affiliation: Department of Breast and Endocrine Surgery, School of Medicine, Tokai University, Isehara, Japan.
authors.forename: Banri
authors.initials: B
authors.lastname: Tsuda
authors.affiliation: Department of Breast and Endocrine Surgery, School of Medicine, Tokai University, Isehara, Japan.
authors.forename: Takuho
authors.initials: T
authors.lastname: Okamura
authors.affiliation: Department of Breast and Endocrine Surgery, School of Medicine, Tokai University, Isehara, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Breast and Endocrine Surgery, School of Medicine, Tokai University, Isehara, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Breast and Endocrine Surgery, School of Medicine, Tokai University, Isehara, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tokuda
mesh_terms: D000328:Adult; D015415:Biomarkers; D001706:Biopsy; D001943:Breast Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging
chemical_list: D015415:Biomarkers
keywords: Immune microenvironment; immunohistochemistry; metastatic breast tumor; primary breast tumor; tumor-infiltrating lymphocytes