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PD-1+ immune cell infiltration inversely correlates with survival of operable breast cancer patients

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Abstract

The programmed death-1 (PD-1) molecule is mainly expressed on functionally “exhausted” CD8+ T cells, dampening the host antitumor immune response. We evaluated the ratio between effective and regulatory T cells (Tregs) and PD-1 expression as a prognostic factor for operable breast cancer patients. A series of 218 newly diagnosed invasive breast cancer patients who had undergone primary surgery at Ruijin Hospital were identified. The influence of CD8+ cytotoxic T lymphocytes, FOXP3+ (Treg cell marker), and PD-1+ immune cell counts on prognosis was analyzed utilizing immunohistochemistry. Both PD-1+ immune cells and FOXP3+ Tregs counts were significantly associated with unfavorable prognostic factors. In bivariate, but not multivariate analysis, high tumor infiltrating PD-1+ cell counts correlated with significantly shorter patient survival. Our results suggest a prognostic value of the PD-1+ immune cell population in such breast cancer patients. Targeting the PD-1 pathway may be a feasible approach to treating patients with breast cancer.

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Abbreviations

PD-1:

Programmed death-1

Treg:

Regulatory T cell

CTL:

Cytotoxic T lymphocyte

NSCLC:

Non-small cell lung cancer

OS:

Overall survival

DFS:

Disease-free survival

BCSS:

Breast cancer-specific survival

TIL:

Tumor-infiltrating lymphocyte

PD-L1:

Programmed death-ligand 1

IHC:

Immunohistochemical

FFPE:

Formalin-fixed paraffin-embedded

H&E:

Hematoxylin and eosin

HPF:

High-powered field

SD:

Standard deviation

IDC:

Invasive ductal carcinoma

ILC:

Invasive lobular carcinoma

SE:

Standard error

ER:

Estrogen receptor

PR:

Progesterone receptor

HER2:

Human epidermal growth factor receptor-2

TNBC:

Triple-negative breast cancer

CAF:

Cancer-associated fibroblast

SOCS1:

Suppressor of cytokine signaling 1

RCC:

Renal cell carcinoma

HR:

Hazard ratio

CI:

Confidence interval

MDSC:

Myeloid-derived suppressor cell

TAM:

Tumor-associated macrophage

ORR:

Overall response rate

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Acknowledgments

Research supported by grants from the National Natural Science Foundation of China (Grant Nos. 81202087; 81172520; 81202088), Leading Academic Discipline Project of Shanghai Municipal Education Commission (Grant No. J50208), and Foundation of Shanghai Science and Technology Commission (Grant No. 12140901503).

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Shanghai Ruijin Hospital, Comprehensive Breast Health Center, Shanghai, 200025, China

    Shenyou Sun, Yan Mao, David H. Garfield, Ou Huang, Long Sun, Qixiang Yu & Kunwei Shen

  2. Linyi People’s Hospital, General Surgery Ward 3, Linyi, 276003, Shandong, China

    Shenyou Sun

  3. Department of Pathology, Shanghai Ruijin Hospital, Shanghai, 200025, China

    Xiaochun Fei, Fei Yuan & Xiaolong Jin

  4. Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Xiumin Wang, Jinglong Wang & Jianhua Wang

  5. Promed Cancer Centers-Shanghai, Shanghai, 200020, China

    David H. Garfield

  6. Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2 Road, Shanghai, China

    Kunwei Shen

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  1. Shenyou Sun
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  2. Xiaochun Fei
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  3. Yan Mao
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  9. Long Sun
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  10. Qixiang Yu
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  11. Xiaolong Jin
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  12. Jianhua Wang
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  13. Kunwei Shen
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Corresponding author

Correspondence to Kunwei Shen.

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Shenyou Sun and Xiaochun Fei have contributed equally to this work.

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Sun, S., Fei, X., Mao, Y. et al. PD-1+ immune cell infiltration inversely correlates with survival of operable breast cancer patients. Cancer Immunol Immunother 63, 395–406 (2014). https://doi.org/10.1007/s00262-014-1519-x

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