Immunotyping of tumor‑infiltrating lymphocytes in triple‑negative breast cancer and genetic characterization

Abstract

Tumor-infiltrating lymphocytes (TILs) reflect the host immune response against cancer cells. Immunomodulators have been recently suggested as a novel therapeutic strategy against triple-negative breast cancer (TNBC). However, the TIL profile in TNBC has not been thoroughly investigated. In the present study, the percentage, immunophenotype and genetic profiles of TILs in pre-surgical tumor samples of patients with TNBC were evaluated prior to neoadjuvant chemotherapy (NAC). Patients diagnosed with breast cancer at Hospital San José TecSalud were consecutively and prospectively enrolled in the present study between August 2011 and August 2015. The pathological response to NAC was evaluated using the de Miller-Payne and MD Anderson Cancer Center system. TIL percentage (low, intermediate, and high) was evaluated using special hematoxylin-eosin staining on the core needle biopsies. The immunophenotype of TILs was assessed by immunohistochemistry (IHC) for CD3 + , CD4 + and CD8 + . In addition, the gene expression profile of CD3, CD4, CD8, CD20, CD45 , forkhead box P3, interleukin 6, programmed cell death 1 and CD274 molecule was assessed in all patients. A total of 26 samples from patients with TNBC prior to NAC were included in the present study. TILs were low in 30.7%, intermediate in 38.4% and elevated in 30.7% of tumors. CD3 + and CD4 + counts were associated with the pathological response to NAC (P=0.04). Finally, an overexpression pattern of CD3, CD4, CD8, CD45 and CD20 genes was observed in patients with a partial or complete pathological response. The present results demonstrated that TILs may predict the pathological response to NAC in patients with TNBC. Furthermore, a more accurate association was identified between the high expression levels of CD3, CD4, CD8, CD45 and CD20 genes and partial and complete pathological response, compared with the association between high expression and IHC alone.

Early Detection and Investigation of Extracellular Vesicles Biomarkers in Breast Cancer

“…It is increasingly necessary to support the study of new biomarkers of angiogenesis and metastatic spread, with the final aim of an accurate disease monitoring targeted towards personalized medicine. In agreement, a study reported a high percentage of patients exhibiting high tumor-infiltrating lymphocytes with CD3 positivity exhibited pathological response to neoadjuvant chemotherapy (Gomez-Μacias et al, 2020). From this point of view, in the future, the herein feasible detection of CD3-positive EVs, potentially secreted by CD-positive infiltrating lymphocytes, could also be investigated and utilized as a marker of response.…”

NUSAP1 and PCLAF (KIA0101) Downregulation by Neoadjuvant Therapy is Associated with Better Therapeutic Outcomes and Survival in Breast Cancer

“…The percentage of tumor-infiltrating lymphocytes (TILs) was assessed following the International TILs Working Group 2014 in breast cancer [ 26 ]. A complete methodology for TIL assessment has been previously described [ 27 ]. Immunohistochemistry for CD3 + , CD4 + , and CD8 + was also performed on the core needle biopsies before NCT to define lymphocyte immunophenotypes, following the American Society of Clinical Oncology/College of American Pathologists guidelines [ 28 ].…”

An Immunohistochemical Study of β-catenin Expression and Immune Cell Population in Metastatic Carcinoma to the Liver

“…Nuclear and/or cytoplasmic expression was taken as overexpression. For CD8 and FoxP3, expression (membranous for CD8 and nuclear for FoxP3) in lymphocytes was quantified as previously described [ 12 , 13 ]. The number of positive-staining cells in five randomly selected high-power fields (Nikon Eclipse 50i 22 mm) were manually counted.…”