Expression of PD-1 on CD4+ Tumor-Infiltrating Lymphocytes in Tumor Microenvironment Associated with Pathological Characteristics of Breast Cancer

Objective. This study aimed to investigate the correlation of CD4+/PD-1+ or CD4+/PD-1− tumor-infiltrating lymphocytes with pathological characteristics in breast cancer patients. Methods. A cross-sectional study consecutively recruited 133 patients with invasive ductal breast cancer. The expression of CD4, programmed cell death protein 1 (PD-1), CK7, CK20, E-cadherin, or Ki-67 was detected by immunohistochemistry. The associations between CD4+/PD-1+ or CD4+/PD-1− tumor-infiltrating lymphocytes and pathological characteristics were evaluated. Results. Elderly patients intended to have a lower level of CD4+/PD-1− tumor-infiltrating lymphocytes (p<0.05). Patients with positive E-cadherin expression had higher median cell counts of CD4+/PD-1− tumor-infiltrating lymphocytes than patients with negative E-cadherin expression (30/HPF versus 10/HPF, p<0.05). Counts of CD4+/PD-1+ tumor-infiltrating lymphocytes had a significant correlation with Ki-67 index that the correlation coefficient was 0.29 (p=0.001). Positive CK20 expression was related to a higher level of CD4+/PD-1− tumor-infiltrating lymphocytes than negative CK20 expression (73/HPF versus 30/HPF, p<0.05). Conclusion. CD4+/PD-1+ or CD4+/PD-1− tumor-infiltrating lymphocytes showed diverse association with pathological features of breast cancer. CD4+/PD-1+ tumor-infiltrating lymphocytes had a significant relationship with Ki-67 expression whereas CD4+/PD-1− tumor-infiltrating lymphocytes had a significant relationship with E-cadherin expression. Further studies are warranted to explore the immunomodulatory effects of phenotypes of CD4+ T cell subsets in breast cancer.

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High expression of E-cadherin and Ki-67 associated with functional/dysfunctional phenotypes of tumor-infiltrating lymphocytes among Chinese patients with operable breast cancer

Journal of International Medical Research ◽

10.1177/0300060518799567 ◽

2018 ◽

Vol 46 (12) ◽

pp. 5219-5227 ◽

Cited By ~ 4

Author(s):

Ruibin Wang ◽

Feng Shi ◽

Lin Zhao ◽

Yanjie Zhao ◽

Guangjiang Wu ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Infiltrating Lymphocytes ◽

Cross Sectional Study ◽

Clinicopathological Features ◽

Chinese Patients ◽

Ki 67 ◽

Cross Sectional ◽

Cell Counts ◽

Infiltrating Lymphocytes ◽

E Cadherin

Objective Breast cancer has become the most common cancer in women in China, and the clinicopathological features differ from those in Western patients. This study was performed to investigate the distribution of programmed cell death protein 1 (PD-1)+/PD-1− tumor-infiltrating lymphocytes (TILs) and its association with clinicopathological features among Chinese patients with breast cancer. Methods In total, 133 consecutive patients with primary breast cancer were recruited into this cross-sectional study from 2012 to 2013. TILs were measured by cell counts under high-power fields (HPFs). Immunohistochemistry was used to detect PD-1 expression on tumor-infiltrating lymphocytes in the microenvironment. Results The median cell counts of the overall TILs, PD-1+ TILs, and PD-1− TILs were 80, 18, and 55/HPF, respectively. The number of PD-1− TILs was significantly lower in older than younger patients (50 vs. 60/HPF). Patients with positive E-cadherin expression had more PD-1− TILs than patients with negative E-cadherin expression (57 vs. 27/HPF). The Ki-67 index was positively correlated with the cell counts of PD-1+ TILs, and the correlation coefficient was 0.29. Conclusions PD-1 expression on TILs had different clinicopathological features in Chinese patients with breast cancer. E-Cadherin expression was associated with PD-1− TILs; however, Ki-67 expression was associated with PD-1+ TILs.

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Cell Counts, rather than Proportion, of CD8/PD-1 Tumor-Infiltrating Lymphocytes in a Tumor Microenvironment Associated with Pathological Characteristics of Chinese Invasive Ductal Breast Cancer

Journal of Immunology Research ◽

10.1155/2019/8505021 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Qingkun Song ◽

Feng Shi ◽

Maya Adair ◽

Hong Chang ◽

Xiudong Guan ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Axillary Lymph Node ◽

Tumor Infiltrating Lymphocytes ◽

Axillary Lymph Node Metastasis ◽

Axillary Lymph ◽

Ki 67 ◽

Invasive Ductal Breast Cancer ◽

Cell Counts ◽

Infiltrating Lymphocytes

Objective. This study is aimed at investigating the association of exhausted CD8+ tumor-infiltrating lymphocytes with clinic-pathological factors. Methods. 133 patients diagnosed with primary invasive ductal breast cancer were recruited into the cross-sectional study consecutively. Immunohistochemistry was used to detect biomarker expression on formalin-fixed and paraffin-embedded sections. Double staining of CD8 and PD-1 was conducted on lymphocytes. Results. The proportion of CD8+/PD-1- TILs was 16% among patients with axillary lymph node metastasis, significantly lower than those without metastasis (24%). The expression of CK7, CK20, or Ki-67 was not related with the proportion of phenotypes of CD8/PD-1 TILs. Younger patients had more cell counts of CD8+/PD-1- TILs than elderly patients (18/HPF vs. 9/HPF, p<0.05). Patients with axillary lymph node metastasis had less CD8+/PD-1- TILs than those without metastasis (11/HPF vs. 27/HPF, p<0.05). Median counts of CD8+/PD-1- TILs among patients with CK20 and E-Cad expression were 33/HPF and 14/HPF, significantly higher than those among patients with negative CK20 (16/HPF) and E-Cad expression (6/HPF). Ki-67 index had a significant correlation with cell counts of CD8+/PD-1+ TILs and CD8+/PD-1- TILs, and the correlation coefficients were 0.19 and 0.21 (p<0.05), respectively. Conclusion. The proportion of CD8+/PD-1- TILs was related with metastatic status of the axillary lymph node but cell counts of CD8+/PD-1- TILs were related with metastatic status of the axillary lymph node and expression of CK7, CK20, E-Cad, and Ki-67. Absolute cell counts, not proportion of CD8/PD-1 TILs, were more likely to distinguish clinic and pathologic characteristics of breast cancer.

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Ki-67 expression of tumor-infiltrating lymphocytes serves as a prognostic factor in Luminal-B breast cancer patients with residual disease after neoadjuvant chemotherapy

The Breast ◽

10.1016/s0960-9776(19)30258-9 ◽

2019 ◽

Vol 44 ◽

pp. S68-S69

Author(s):

R.-X. Wang ◽

S. Chen ◽

Z.-M. Shao

Keyword(s):

Breast Cancer ◽

Prognostic Factor ◽

Neoadjuvant Chemotherapy ◽

Cancer Patients ◽

Residual Disease ◽

Tumor Infiltrating Lymphocytes ◽

Breast Cancer Patients ◽

Ki 67 ◽

Luminal B ◽

Infiltrating Lymphocytes

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CD8+ tumor infiltrating lymphocytes strongly correlate with molecular subtype and clinico-pathological characteristics in breast cancer patients from Sudan

Translational Medicine Communications ◽

10.1186/s41231-016-0005-1 ◽

2016 ◽

Vol 1 (1) ◽

Cited By ~ 3

Author(s):

Mahmoud Mohamed ◽

Hina Sarwath ◽

Nada Salih ◽

Devendra Bansal ◽

Prem Chandra ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Molecular Subtype ◽

Tumor Infiltrating Lymphocytes ◽

Breast Cancer Patients ◽

Pathological Characteristics ◽

Infiltrating Lymphocytes

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Stromal Tumor Infiltrating Lymphocytes (sTILs) as a putative prognostic marker to identify a responsive subset of TNBC in an Indian Breast Cancer Cohort.

10.1101/2020.08.19.20177865 ◽

2020 ◽

Author(s):

Pooja Vaid ◽

Anirudha Puntambekar ◽

Rituja Banale ◽

Ruhi Reddy ◽

Rohini Unde ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Prognostic Significance ◽

Disease Free Survival ◽

Tumor Infiltrating Lymphocytes ◽

Response To Therapy ◽

Stromal Tumor ◽

Breast Cancer Patients ◽

Infiltrating Lymphocytes ◽

Disease Free

Objectives Prognostic significance of stromal tumor infiltrating lymphocytes; sTILs is evaluated to identify a responsive subset of TNBC in an Indian cohort of breast cancer patients. Methods A retrospective cohort of breast cancer patients from a single onco-surgeon breast cancer clinic treated with uniform treatment strategy across is evaluated for sTILs. FFPE tissue of primary tumor of invasive breast carcinoma are collected with ethical approvals. Tumor sections blinded for subtypes are stained with H&E and scored for sTILs by a pathologist following Immuno-Oncology TILs working groups scoring guidelines. Results Analysis of 144 primary breast tumors for sTILs scores re-enforces significantly higher infiltration in TNBC tumors than HER2+ve and ER+ve tumors. Higher sTILs scores co-relate with gradually incremental pathological response to therapy specifically in TNBC subset and with better disease-free survival outcomes. Within TNBC, older and post-menopausal patients harbor higher scores of sTILs. Conclusion Despite a small cohort of breast cancer patients, TNBC subtype reflected significantly higher scores of sTILs with better response to therapy and disease-free outcomes as compared to other breast cancer subtypes. A larger number of breast cancer patients from an Indian cohort will strengthen the findings to establish sTILs as a marker to identify a responsive subset of TNBC.

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