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Clin Breast Cancer. 2016 Feb;16(1):51-8. doi: 10.1016/j.clbc.2015.07.006. Epub 2015 Aug 6.

Prognostic Implications of Tumor-Infiltrating Lymphocytes in Association With Programmed Death Ligand 1 Expression in Early-Stage Breast Cancer.

Author information

1
Center for Breast Cancer, National Cancer Center, Goyang-si, Korea; Breast and Endocrine Center Branch of Research Institute, National Cancer Center, Goyang-si, Korea.
2
Translational Epidemiology Branch, Division of Cancer Epidemiology and Prevention, Research Institute, National Cancer Center, Goyang-si, Korea; Department of Laboratory Medicine, Center for Diagnostic Oncology, Hospital and Research Institute, National Cancer Center, Goyang-si, Korea.
3
Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Weill Medical College of Cornell University, Houston, TX.
4
Breast and Endocrine Center Branch of Research Institute, National Cancer Center, Goyang-si, Korea.
5
Center for Breast Cancer, National Cancer Center, Goyang-si, Korea.
6
Biometric Research Branch, National Cancer Center, Goyang-si, Korea.
7
Center for Breast Cancer, National Cancer Center, Goyang-si, Korea; Breast and Endocrine Center Branch of Research Institute, National Cancer Center, Goyang-si, Korea. Electronic address: jungsro@ncc.re.kr.

Abstract

BACKGROUND:

The immune system might influence breast cancer (BC) prognosis. However, the relationship between programmed death ligand 1 (PD-L1) and tumor-infiltrating lymphocyte (TIL) profiles remains unclear with respect to BC subtypes.

PATIENTS AND METHODS:

We investigated the relationship between TIL profiles for CD8+ and forkhead box P3-positive (FOXP3+) and PD-L1 expression in primary tumor tissue using immunohistochemistry and the clinical outcomes in 2 patient cohorts at the National Cancer Center: 256 patients diagnosed with early-stage BC from January 2001 to December 2005 and 77 hormone receptor (HR)-negative BC patients diagnosed from January 2006 to December 2008. Clinical data were collected, including HR status, human epidermal growth factor receptor 2 expression, disease-free survival, and overall survival (OS).

RESULTS:

The median patient age was 47 years (range, 28-78), and the median follow-up period was 9.8 years. Of the 333 patients, 186 (55.9%) had HR-positive and 125 (37.5%) had node-positive BC. We found a strong positive correlation between CD8+ TILs and FOXP3+ TILs (P < .001). CD8+ TILs were more abundant in tumors with low PD-L1 expression (P < .001), although no association was found between FOXP3+ TILs and PD-L1 expression. More CD8+ TILs were present in HR-negative than in HR-positive BC (P < .001), and PD-L1 expression was more frequent in HR-positive BC (P < .001). A greater number of CD8+ TILs (increase in quartile) was strongly associated with OS (hazard ratio, 0.61; 95% confidence interval, 0.39-0.95; P = .03) only in HR-negative BC when adjusted for various clinical factors. PD-L1 expression and FOXP3+ TILs did not exhibit such associations.

CONCLUSION:

Higher CD8+ lymphocyte infiltration was related to lower PD-L1 expression and higher FOXP3+ TIL infiltration in BC. Higher CD8+ TIL expression was associated with prolonged survival only in those with HR-negative BC.

KEYWORDS:

Hormone receptor; Immunohistochemistry; PD-L1; Prognosis; Tumor infiltrating lymphocytes

PMID:
26364145
DOI:
10.1016/j.clbc.2015.07.006
[Indexed for MEDLINE]

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