Nomogram to Predict Tumor-Infiltrating Lymphocytes in Breast Cancer Patients

Background: Tumor-infiltrating lymphocytes (TILs) play important roles in the prediction of prognosis and neoadjuvant therapy (NAT) efficacy in breast cancer (BRCA) patients, in this study, we identified clinicopathological factors related to BRCA TILs, then to construct and validate nomogram to predict high density of TILs.Methods: A total of 826 patients diagnosed with BRCA in Sun Yat-Sen University cancer center were enrolled in nomogram cohort. TILs were assessed using hematoxylin-eosin (H&E) staining by two pathologists. Complete clinical data were collected for analysis. Then the enrolled patients were split into a training set and validation set at a ratio of 8:2. and the backward multivariate binary logistic regression model was used to establish nomogram for predicting BRCA TILs, which were further evaluated and validated using the C-index, receiver operating characteristic (ROC) curves and calibration curves. Then another independent NAT cohort of 106 patients was established for verifying this nomogram in NAT efficacy prediction.Results: TILs were significantly correlated with body mass index (BMI), tumor differentiation, ER, PR, HER2 expression, Ki67, blood biochemical indicators including total bilirubin (TBIL), indirect bilirubin (IBIL), total protein (TP), Globulin (GLOB), inorganic phosphorus (IP), calcium (Ca). In which ER expression level [OR = 0.987, 95%CI (0.982–0.992), p < 0.001], IP [OR = 4.462, 95%CI (1.171∼17.289), p = 0.029], IBIL [OR = 0.906, 95%CI (0.845–0.966), p = 0.004] and TP [OR = 1.053, 95%CI (1.010–1.098, p = 0.016)] were independent predictors of TILs. Then nomogram was established, for which calibration curves (C-index = 0.759) and ROC curve (AUC = 0.759, 95%CI 0.717–0.801) in training sets, calibration curves (C-index = 0.708) and ROC curve (AUC = 0.708, 95%CI 0.617–0.800) in validation sets demonstrated great evaluation efficiency. Besides, independent NAT cohort verified this nomogram can distinguish patients with greater NAT efficacy (p = 0.041).Conclusion: The finds of clinicopathological factors associated with TILs could help clinicians to understand the tumor immunity of BRCA and improve treatment system for patients, and the established nomogram with high evaluation efficiency may be used as a complement tool for distinguishing patients with better NAT efficacy.

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

Journal of Immunology Research ◽

10.1155/2018/5690258 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Yan-Jie Zhao ◽

Jian Zhang ◽

Feng Shi ◽

Zhi-Ping Hu ◽

Jiang-Ping Wu ◽

...

Keyword(s):

Breast Cancer ◽

Significant Relationship ◽

Tumor Infiltrating Lymphocytes ◽

T Cell Subsets ◽

Breast Cancer Patients ◽

Ki 67 ◽

Pathological Characteristics ◽

Cell Counts ◽

Infiltrating Lymphocytes ◽

E Cadherin

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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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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