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

In Hae Park; Sun Young Kong; Jae Yoon Ro; Youngmee Kwon; Joo Hyun Kang; Hye Jin Mo; So Youn Jung; Seeyoun Lee; Keun Seok Lee; Han Sung Kang; Eunsook Lee; Jungnam Joo; Jungsil Ro

doi:10.1016/j.clbc.2015.07.006

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

In Hae Park, Sun Young Kong, Jae Yoon Ro, Youngmee Kwon, Joo Hyun Kang, Hye Jin Mo, So Youn Jung, Seeyoun Lee, Keun Seok Lee, Han Sung Kang, Eunsook Lee, Jungnam Joo, Jungsil Ro

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77 Scopus citations

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.

Original language	English (US)
Pages (from-to)	51-58
Number of pages	8
Journal	Clinical Breast Cancer
Volume	16
Issue number	1
DOIs	https://doi.org/10.1016/j.clbc.2015.07.006
State	Published - Feb 1 2016

Keywords

Hormone receptor
Immunohistochemistry
PD-L1
Prognosis
Tumor infiltrating lymphocytes

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.clbc.2015.07.006

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Park, I. H., Kong, S. Y., Ro, J. Y., Kwon, Y., Kang, J. H., Mo, H. J., Jung, S. Y., Lee, S., Lee, K. S., Kang, H. S., Lee, E., Joo, J., & Ro, J. (2016). Prognostic Implications of Tumor-Infiltrating Lymphocytes in Association with Programmed Death Ligand 1 Expression in Early-Stage Breast Cancer. Clinical Breast Cancer, 16(1), 51-58. https://doi.org/10.1016/j.clbc.2015.07.006

@article{0e29796fad8846a3b863843f0eeac275,

title = "Prognostic Implications of Tumor-Infiltrating Lymphocytes in Association with Programmed Death Ligand 1 Expression in Early-Stage Breast Cancer",

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",

author = "Park, {In Hae} and Kong, {Sun Young} and Ro, {Jae Yoon} and Youngmee Kwon and Kang, {Joo Hyun} and Mo, {Hye Jin} and Jung, {So Youn} and Seeyoun Lee and Lee, {Keun Seok} and Kang, {Han Sung} and Eunsook Lee and Jungnam Joo and Jungsil Ro",

note = "Funding Information: The present study was supported by the Korean National Cancer Center (grant NCCNCS12657 ). We thank all the participants in our study. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc. All rights reserved.",

year = "2016",

month = feb,

day = "1",

doi = "10.1016/j.clbc.2015.07.006",

language = "English (US)",

volume = "16",

pages = "51--58",

journal = "Clinical Breast Cancer",

issn = "1526-8209",

publisher = "Elsevier",

number = "1",

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T1 - Prognostic Implications of Tumor-Infiltrating Lymphocytes in Association with Programmed Death Ligand 1 Expression in Early-Stage Breast Cancer

AU - Park, In Hae

AU - Kong, Sun Young

AU - Ro, Jae Yoon

AU - Kwon, Youngmee

AU - Kang, Joo Hyun

AU - Mo, Hye Jin

AU - Jung, So Youn

AU - Lee, Seeyoun

AU - Lee, Keun Seok

AU - Kang, Han Sung

AU - Lee, Eunsook

AU - Joo, Jungnam

AU - Ro, Jungsil

N1 - Funding Information: The present study was supported by the Korean National Cancer Center (grant NCCNCS12657 ). We thank all the participants in our study. Publisher Copyright: © 2016 Elsevier Inc. All rights reserved.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - 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.

AB - 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.

KW - Hormone receptor

KW - Immunohistochemistry

KW - PD-L1

KW - Prognosis

KW - Tumor infiltrating lymphocytes

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

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Keywords

ASJC Scopus subject areas

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