Heterogeneity of tumour-infiltrating lymphocytes in breast cancer and its prognostic significance.

Tumour-infiltrating lymphocytes (TILs) in breast cancer (BC) provide prognostic and predictive information. The aim of this study was to assess the spatial and temporal heterogeneity of TILs in BC and its relationship with immune cell subtypes. Immunohistochemically defined immune cell subtypes, i.e. those expressing T-cell markers (CD3, CD8, and FOXP3), a B-cell marker (CD20) and a histiocytic marker (CD68), were evaluated in a large series (n = 1165) of invasive BCs. A subset of full-face haematoxylin and eosin (H&E)-stained slides were examined for TILs heterogeneity within primary tumours and the corresponding local recurrent carcinomas to investigate spatial and temporal TILs heterogeneity. H&E-stained sections from multiple tumour blocks (three or four blocks per case) representing different tumour areas were evaluated to assess TILs interslide heterogeneity and intraslide heterogeneity. Both average stromal TILs (AV-TILs) and hotspot stromal TILs (HS-TILs) were assessed. AV-TILs showed associations with all immune cell subtypes; however, CD3+ cells constituted the main component (mean number of CD3+ was 55), whereas CD20+ cells constituted the smallest component (mean number of CD20 was 13). There was no significant statistical difference between TILs across tumour blocks of the same case (P = 0.251 for AV-TILs and P = 0.162 for HS-TILs). Triple-negative breast cancer (TNBC) showed higher TILs percentage than other BC subtypes (P < 0.001). High AV-TILs, CD3+ cells, CD8+ cells and CD20+ cells were associated with longer survival in TNBC patients (P < 0.05). High AV-TILs in recurrent tumours showed a significant association with shorter post-recurrence survival (P = 0.004). Despite the heterogeneity of immune cell type components, average TILs in one full-face H&E-stained section reliably represent TILs in the whole tumour. TILs were associated with outcome in TNBC patients, as well as having prognostic significance for recurrent tumours.

Althobiti M ，Aleskandarany MA ，Joseph C ，Toss M ，Mongan N ，Diez-Rodriguez M ，Nolan CC ，Ashankyty I ，Ellis IO ，Green AR ，Rakha EA ... -  《-》

Morphological Evaluation of Tumor-Infiltrating Lymphocytes (TILs) to Investigate Invasive Breast Cancer Immunogenicity, Reveal Lymphocytic Networks and Help Relapse Prediction: A Retrospective Study.

Romagnoli G ，Wiedermann M ，Hübner F ，Wenners A ，Mathiak M ，Röcken C ，Maass N ，Klapper W ，Alkatout I ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Integration of tumour infiltrating lymphocytes, programmed cell-death ligand-1, CD8 and FOXP3 in prognostic models for triple-negative breast cancer: Analysis of 244 stage I-III patients treated with standard therapy.

Tumour infiltrating lymphocytes (TILs) are an established prognostic biomarker for triple-negative breast cancer (TNBC). We evaluated the role of programmed cell-death ligand-1 (PD-L1), CD8 and FOXP3 expression in refining a prognostic model for non-metastatic TNBC beyond classic factors and TILs. Primary tumour samples from 244 early patients with TNBC, all treated with surgery and chemotherapy, were collected. Stromal TILs were evaluated on haematoxylin-eosin slides according to guidelines. PD-L1, CD8 and FOXP3 were assessed by immunohistochemistry and evaluated by digital pathology. TILs, PD-L1, CD8 and FOXP3 were positively correlated with each other (P < 0.001). TILs were confirmed as an independent prognostic factor. When PD-L1, CD8 and FOXP3 were added to multivariable models including classic factors (age, stage, histologic grade) and TILs, PD-L1 provided the largest amount of additional prognostic information: likelihood ratio χ2 4.60, P = 0.032 (in a model including classic factors and TILs 10% increments) and likelihood ratio χ2 6.50, P = 0.011 (in a model including classic factors and TILs >30% versus <30%). In the subset of patients treated with neoadjuvant chemotherapy, FOXP3 provided further prognostic information beyond classic factors, TILs and pathological complete response (pCR) (likelihood ratio χ2 5.01, P = 0.025). For patients who did not achieve a pCR, the expression of CD8 and PD-L1 was significantly increased from baseline to residual disease. Beyond clinicopathological factors and TILs, other immune biomarkers may add prognostic information for early TNBC. The increased PD-L1 expression on residual disease after neoadjuvant chemotherapy strengthens the rationale of testing immune checkpoint inhibitors in the post-neoadjuvant setting.

Dieci MV ，Tsvetkova V ，Griguolo G ，Miglietta F ，Tasca G ，Giorgi CA ，Cumerlato E ，Massa D ，Lo Mele M ，Orvieto E ，Guarneri V ，Conte P ... -  《-》

The therapeutic candidate for immune checkpoint inhibitors elucidated by the status of tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression in triple negative breast cancer (TNBC).

Tomioka N ，Azuma M ，Ikarashi M ，Yamamoto M ，Sato M ，Watanabe KI ，Yamashiro K ，Takahashi M ... -  《-》

Tumor-infiltrating B cells and T cells correlate with postoperative prognosis in triple-negative carcinoma of the breast.

Kuroda H ，Jamiyan T ，Yamaguchi R ，Kakumoto A ，Abe A ，Harada O ，Masunaga A ... -  《BMC CANCER》