Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Immune Microenvironment and PD-L1 Expression in Breast Cancer: A Review of Current Evidence and Prognostic Implications from Pathologist’s Perspective

Giuseppe Angelico
* ORCID logo ,
Giuseppe Broggi
ORCID logo ,
Giordana Tinnirello
ORCID logo ,
Lidia Puzzo
ORCID logo ,
Giada Maria Vecchio
ORCID logo ,
Lucia Salvatorelli
,
Lorenzo Memeo
ORCID logo ,
Angela Santoro
ORCID logo ,
Gaetano Magro
,
Rosario Caltabiano
ORCID logo
Version 1 : Received: 6 June 2023 / Approved: 7 June 2023 / Online: 7 June 2023 (08:04:20 CEST)

A peer-reviewed article of this Preprint also exists.

Angelico, G.; Broggi, G.; Tinnirello, G.; Puzzo, L.; Vecchio, G.M.; Salvatorelli, L.; Memeo, L.; Santoro, A.; Farina, J.; Mulé, A.; Magro, G.; Caltabiano, R. Tumor Infiltrating Lymphocytes (TILS) and PD-L1 Expression in Breast Cancer: A Review of Current Evidence and Prognostic Implications from Pathologist’s Perspective. Cancers 2023, 15, 4479. Angelico, G.; Broggi, G.; Tinnirello, G.; Puzzo, L.; Vecchio, G.M.; Salvatorelli, L.; Memeo, L.; Santoro, A.; Farina, J.; Mulé, A.; Magro, G.; Caltabiano, R. Tumor Infiltrating Lymphocytes (TILS) and PD-L1 Expression in Breast Cancer: A Review of Current Evidence and Prognostic Implications from Pathologist’s Perspective. Cancers 2023, 15, 4479.

Abstract

With the rise of novel immunotherapies able to stimulate the antitumor immune response, increasing literature data concerning the immunogenicity of breast cancer have been published in recent years. Numerous clinical studies have been conducted in order to identify novel biomarkers that could reflect the immunogenicity of BC and predict response to immunotherapy. In this regard, TILs have emerged as an important immunological biomarker related to the antitumor immune re-sponse in BC. TILs are more frequently observed in triple-negative breast cancer and HER2+ sub-types where increased TIL levels have been linked to better response to neoadjuvant chemotherapy and with improved survival. PD-L1 is a type 1 transmembrane protein ligand expressed on T lymphocytes, B lymphocytes and antigen-presenting cells and is considered a key inhibitory checkpoint involved in cancer immune regulation. PD-L1 immunohistochemical expression in breast cancer is observed in about 10–30% of cases and is extremely variable based on tumor stage and molecular subtypes . In detail, TNBC shows the highest percentages of PD-L1 positivity, followed by HER2+ tumors. On the other hand, PD-L1 is rarely expressed (0-10% of cases) in hormone-receptor positive BC. The prognostic role of PD-L1 expression in BC is still controversial since different immunohistochemistry (IHC) clones, cut-off points and scoring systems have been utilized across published studies. In the present paper an extensive review on the current knowledge of immune landscape of BC is provided. In detail TILS and PD-L1 expression across different BC subtypes is discussed also providing a guide for their pathological assessment and reporting.

Keywords

breast cancer; TILs; PD-L1; immunotherapy; chemotherapy, triple negative breast cancer; HER2; luminal breast cancer; CPS

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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