scholarly journals Influence of mutagenic versus non-mutagenic pre-operative chemotherapy on the immune infiltration of breast cancer

2018 ◽  
Author(s):  
Anna-Mária Tőkés ◽  
Orsolya Rusz ◽  
Gábor Cserni ◽  
Erika Tóth ◽  
Gábor Rubovszky ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Tumor Infiltrating Lymphocytes ◽  
Distant Metastases ◽  
Chemotherapeutic Agents ◽  
Hazard Ratio ◽  
Stromal Tumor ◽  
Survival Analyses ◽  
The Difference ◽  
Pre Treatment ◽  
Infiltrating Lymphocytes

AbstractBackgroundChemotherapeutic agents are often mutagenic. Induction of mutation associated neo-epitopes is one of the mechanisms by which chemotherapy is thought to increase the number of tumor-infiltrating lymphocytes, but the clinical relevance of this triggered immune response is not known.We decided to investigate, whether treatment with various chemotherapeutic agents with significantly different mutagenic capacity induce a significantly different number of stromal tumor-infiltrating lymphocytes (StrTIL) in the clinical setting.Methods112 breast carcinoma cases treated with pre-operative chemotherapy were selected for the study. According to chemotherapy regimen 28/112 patients received platinum-based, 42/112 cyclophosphamide-based and 42/112 anthracycline-based chemotherapy. The percentage of stromal tumor-infiltrating lymphocytes (StrTIL) was evaluated on hematoxylineosin stained slides of pre-treatment core biopsy (pre-StrTIL) and post-treatment surgical tumor samples (post-StrTIL), according to the most recent recommendation of International TILs Working Group. In survival analyses, TIL changes (ΔStrTIL) were calculated from the difference between post-StrTIL and pre-StrTIL.ResultsOf the 112 cases, 58.0% (n=65) were hormone receptor (HR) positive and 42.0% (n=47) were HR negative. There was a trend of higher post-StrTIL compared to pre-StrTIL (median 6.25% vs. 3.00%; p<0.001). When analyzing the pre-StrTIL and post-StrTIL among the three treatment groups, we experienced significant StrTIL increase independently of the treatment applied. Based on the results of survival analyses both post-StrTIL and ΔStrTIL was found to be independent prognostic factor in HR negative cases. Each 1% increase in post-StrTIL reduced the hazard of distant metastases development by 2.6% (hazard ratio: 0.974; CI: 0.948-1.000; p=0.05) and for each 1% ΔStrTIL increment, the risk of distant metastases was reduced by 4.3% (hazard ratio: 0.957; CI: 0.932-0.983; p=0.001). The prognostic role of StrTIL in HR positive cases could not be proven.ConclusionsStrTIL expression might be stimulated by highly (platinum), moderately (cyclophosphamide) and marginally (taxane, anthracycline) mutagenic chemotherapeutic agents. Increase in StrTIL in residual cancer compared to pre-treatment tumor tissue is associated with improved distant metastasis-free survival in cases with HR negative breast carcinoma.

The value of tumor-infiltrating lymphocytes and CD8 expression as a predictor of response to anthracycline-based neoadjuvant chemotherapy in invasive breast carcinoma of no special type

2021 ◽  
pp. 1-6
Author(s):  
Upik A. Miskad ◽  
Rizki A. Rifai ◽  
Rina Masadah ◽  
Berti Nelwan ◽  
Djumadi Ahmad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Breast Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Predictive Value ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Invasive Breast Carcinoma ◽  
Study Results ◽  
Infiltrating Lymphocytes

BACKGROUND: The immune system is known to play an important role in tumor cell eradication. Although cancer cells were able to escape from the immune system, many studies showed mononuclear inflammatory cell infiltrates known as tumor-infiltrating lymphocytes (TILs) on breast cancer histopathology specimens showed better prognosis, including in disease-free survival (DFS) and chemotherapy responses. OBJECTIVE: This study aimed to reveal the predictive value of tumor-infiltrating lymphocytes (TILs) levels and CD8 expression in invasive breast carcinoma of no special type patients’ samples on response to anthracycline-based neoadjuvant chemotherapy. METHODS: 75 pre-treatment biopsy samples that were diagnosed as invasive breast carcinoma of no special type were evaluated. TILs level determined following recommendations of International TILs Working Group 2014, CD8 expression assessed semiquantitatively after immunohistochemistry staining. Response to anthracycline-based neoadjuvant chemotherapy evaluated clinically using Response Evaluation Criteria in Solid Tumours (RECIST) criteria and pathologically by evaluating hematoxylin and eosin (H&E)-stained slides from mastectomy specimens after 3 or 4 cycles of neoadjuvant chemotherapy. RESULTS: Chi-squared analysis showed a significant relationship between TILs level and CD8 expression with chemotherapy responses clinically (p = 0.011 and p = 0.017 respectively) but not pathologically. Furthermore, the logistic regression test exhibit the predictive value of TILs level was 66.7% and CD8 expression was 64%. CONCLUSIONS: This study results suggest that TILs level and CD8 expression may be added as predictive factors to the response of anthracycline-based neoadjuvant chemotherapy, and oncologists may take benefit in breast cancer patient’s management.

Multiparameter study of the immunophenotype of tumor infiltrating lymphocytes, in cancer patients

2016 ◽  
Vol 21 (1-2) ◽  
pp. 51-54 ◽  
Author(s):  
Tat’yana N. Zabotina ◽  
O. V Korotkova ◽  
A. A Borunova ◽  
D. V Tabakov ◽  
I. I Bokin ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Solid Tumors ◽  
Squamous Carcinoma ◽  
Tumor Infiltrating Lymphocytes ◽  
Tissue Level ◽  
Main Role ◽  
Regulatory T Lymphocytes ◽  
The Difference ◽  
Infiltrating Lymphocytes ◽  
First Time

For the first time in Russia the immunophenotype of tumor infiltrated lymphocytes (TIL) was investigated with the use of a method of quantitative flow cytometry. Samples from 104 patients, suffering from solid tumors (such as breast cancer, ovarian cancer, melanoma and oral cavity squamous carcinoma), were analyzed in this investigation. In the difference of cytomorphological analysis, the method of flow cytometry identified TIL in 100% of cases. In the structure of CDS+Т- lymphocytes the ratio CD4/CD8 was equal to 1,1±0,1. Serial gating strategy allowed to assess minor subpopulations of regulatory T-lymphocytes CD45+CD4+CD127+low/neg and CD45+CD8+CD28-CD11b-. Regulatory mechanisms with involvement of CD8 T-cells played the main role in the generation of immune responses at the tissue level ofpatients, suffering from solid tumors, independent of nosological form of disease.

Tumor infiltrating lymphocytes (TIL) to predict response to neoadjuvant chemotherapy in breast cancer: A systemic review and meta-analysis.

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 138-138 ◽  
Author(s):  
Yan Mao ◽  
Qing Qu ◽  
Yuzi Zhang ◽  
Junjun Liu ◽  
Kunwei Shen
Keyword(s):  
Breast Cancer ◽  
T Lymphocytes ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Meta Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Pathological Response ◽  
Pre Treatment ◽  
Infiltrating Lymphocytes ◽  
The Relationship

138 Background: Whether tumor-infiltrating lymphocytes (TILs) predict response to neoadjuvant chemotherapy (NAC) remains elusive. Methods: A systematic review and meta-analysis was undertook to establish the relationship between TIL and pathological complete response (pCR) rate in NAC of breast cancer. A PubMed and Web of Science literature search was designed. Studies were included, in which the predictive significance of intratumoral and/or stromal TIL, and/or CD3+, CD4+, CD8+, and FOXP3+ lymphocytes were determined . Pooled ORs and publication bias was evaluated by STATA software. Results: A total of 13 published studies (including 3,555 patients) were eligible. In pooled analysis, higher number of TIL in pre-treatment biopsy was correlated with higher pCR rate of neoadjuvant chemotherapy, and odds ratio (OR) was 3.82 (95% confidence interval (CI), 3.10-4.70), no matter tested in intratumor (OR=3.32, 95% CI: 2.52-4.37), in stroma (OR=4.15,95% CI: 2.94-5.86), or in combined sites (OR=8.98, 95% CI: 3.79,21.30). Moreover, TIL predicts higher pCR rate in triple negative (OR=5.03,95% CI: 2.31-10.97) and HER2+ (OR=5.54,95% CI: 1.39-22.12) patients, but not in hormonal receptor (HR) +/HER2- patients (OR=2.57, 95% CI: 0.20-33.24). For TIL subsets, CD8+ T-lymphocytes predict better pathological response to NAC no matter in pre- (OR=3.36,95%CI: 1.15-9.85) or post-NAC (OR=4.71,95%CI: 1.29-17.27) tissue, while FOXP3+ T-lymphocytes have similar predictive roles only when tested after NAC (OR=4.26, 95%CI: 1.83-9.92).With limited study, the predictive role of CD3+ and CD4+T-lymphoctes were unclear, more perspective studies were needed in future to establish the relationship. Conclusions: High level of TIL in pre-treatment biopsy could be a good marker indicates better pathological response to NAC in triple-negative and HER2+ breast cancer patients. Different subsets have different predictive roles in the pCR rate to NAC. However, significant heterogeneity and an insufficient number of studies underscore the need for further prospective studies on subsets of T lymphocytes and different subtypes of breast cancer to increase the robustness of the analyses.

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