PD-L1 Expression after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancers Is Associated with Aggressive Residual Disease, Suggesting a Potential for Immunotherapy

Grandal, Beatriz; Mangiardi-Veltin, Manon; Laas, Enora; Laé, Marick; Meseure, Didier; Bataillon, Guillaume; El-Alam, Elsy; Darrigues, Lauren; Dumas, Élise; Daoud, Eric; Vincent‐Salomon, Anne; Talagrand, Laure-Sophie; Pierga, Jean‐Yves; Reyal, Fabien; Hamy, Anne-Sophie

doi:10.3390/cancers13040746

Cited by 11 publications

(10 citation statements)

References 62 publications

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“…The PD-L1 status is also strongly modulated by treatment, with a conversion rate (from positive to negative and vice versa) ranging from 25 to 30% over time [39]. In particular, after neoadjuvant chemotherapy (NACT), PD-L1 expres-sion has been demonstrated to be considerably expressed on a residual disease sample [40] consistent with the observations of CT inducing an adaptive immune response [41].…”

Section: Breast Cancer "Immunogram" Predictors Of Response To Immune-...supporting

confidence: 63%

Immune-Based Therapy in Triple-Negative Breast Cancer: From Molecular Biology to Clinical Practice

Carlino

Diana²,

Piccolo

et al. 2022

Cancers

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Triple-negative breast cancer (TNBC) has been considered for many years an orphan disease in terms of therapeutic options, with conventional chemotherapy (CT) still representing the mainstay of treatment in the majority of patients. Although breast cancer (BC) has been historically considered a “cold tumor”, exciting progress in the genomic field leading to the characterization of the molecular portrait and the immune profile of TNBC has opened the door to novel therapeutic strategies, including Immune Checkpoint Inhibitors (ICIs), Poly ADP-Ribose Polymerase (PARP) inhibitors and Antibody Drug Conjugates (ADCs). In particular, compared to standard CT, the immune-based approach has been demonstrated to improve progression-free survival (PFS) and overall survival (OS) in metastatic PD-L1-positive TNBC and the pathological complete response rate in the early setting, regardless of PD-L1 expression. To date, PD-L1 has been widely used as a predictor of the response to ICIs; however, many patients do not benefit from the addition of immunotherapy. Therefore, PD-L1 is not a reliable predictive biomarker of the response, and its accuracy remains controversial due to the lack of a consensus about the assay, the antibody, and the scoring system to adopt, as well as the spatial and temporal heterogeneity of the PD-L1 status. In the precision medicine era, there is an urgent need to identify more sensitive biomarkers in the BC immune oncology field other than just PD-L1 expression. Through the characterization of the tumor microenvironment (TME), the analysis of peripheral blood and the evaluation of immune gene signatures, novel potential biomarkers have been explored, such as the Tumor Mutational Burden (TMB), Microsatellite Instability/Mismatch Repair Deficiency (MSI/dMMR) status, genomic and epigenomic alterations and tumor-infiltrating lymphocytes (TILs). This review aims to summarize the recent knowledge on BC immunograms and on the biomarkers proposed to support ICI-based therapy in TNBC, as well as to provide an overview of the potential strategies to enhance the immune response in order to overcome the mechanisms of resistance.

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Section: Breast Cancer "Immunogram" Predictors Of Response To Immune-...supporting

confidence: 63%

Immune-Based Therapy in Triple-Negative Breast Cancer: From Molecular Biology to Clinical Practice

Carlino

Diana²,

Piccolo

et al. 2022

Cancers

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“…Previous studies revealed that immune checkpoint regulators were correlated with many biological processes, thus affecting the clinical outcomes of cancer patients (21,22). It is suggested that immune checkpoints could act as markers to predict the prognosis of many cancers, including renal cell carcinoma, lung cancer, and breast cancer (23)(24)(25). However, the prognostic value of immune checkpoints and their association with immune infiltration of KIRC remain unclear.…”

Section: Discussionmentioning

confidence: 99%

Identification of the Prognosis Value and Potential Mechanism of Immune Checkpoints in Renal Clear Cell Carcinoma Microenvironment

Liao

Wang

2021

Front. Oncol.

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BackgroundKidney Renal Clear Cell Carcinoma (KIRC) is one of the most prevalent types of cancer worldwide. KIRC has a poor prognosis and, to date, immunotherapy based on immune checkpoints is the most promising treatment. However, the role of immune checkpoints in KIRC remains ambiguous.MethodsBioinformatics analyses and qRT-PCR were performed to explore and further confirm the prognostic value of immune checkpoint genes and their correlation with immune infiltration in KIRC samples.ResultsThe expression of the immune checkpoint genes CD274, PDCD1LG2, HAVCR2, CTLA4, TIGFT, LAG3, and PDCD1 was upregulated in KIRC tissues. These genes were involved in the activation of the apoptosis pathway in KIRC. Low expression of CD274 and HAVCR2 and high expression of CTLA4 were associated with poor overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) of KIRC patients. The univariate and multivariate analyses revealed that CTLA4, HAVCR2, age, pTNM stage, and tumor grade were independent factors affecting the prognosis of KIRC patients. A predictive nomogram demonstrated that the calibration plots for the 3‐year and 5‐year OS probabilities showed good agreement compared to the actual OS of KIRC patients. The expression of CTLA4 and HAVCR2 were positively associated with immune cell infiltration, immune biomarkers, chemokines, and chemokine receptors. Moreover, miR-20b-5p was identified as a potential miRNA target of CTLA4 in KIRC.ConclusionOur study clarified the prognostic value of several immune checkpoint regulators in KIRC, revealing a CTLA4/miR-20b-5p axis in the control of immune cell infiltration in the tumor microenvironment.

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“…18 Increasing evidences have shown that certain immune checkpoints could serve as prognostic biomarkers or the in some cancers, including renal cell carcinoma, STAD, non-small cell lung cancer and triple-negative breast cancers. 19 , 20 However, the specific role of these immune checkpoints in the prognosis and therapy of STAD were still far from clarified. Therefore, this study aims to clarify the expression and prognosis of these immune checkpoints and their relationship with immune infiltration in STAD.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Prognostic Value and Immune Function of Immune Checkpoints in Stomach Adenocarcinoma

Shen¹,

Liu²

2021

IJGM

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Background Stomach adenocarcinoma (STAD) is one of the most prevalent malignances and ranks fifth in incidence and third in the cancer-related deaths among all malignances. The prognosis of STAD is poor. Immunotherapy based on immune checkpoint blockade is ever-increasingly suggested as the most promising therapy strategy for STAD. However, the prognosis and therapy value of immune checkpoints in STAD is far from clarified. Methods In our study, bioinformatics methods were performed to explore the expression and prognosis value of immune checkpoints in STAD and their association with immune infiltration. qRT-PCR was performed to verify our result. Results Most of the immune checkpoints were upregulated in STAD. There were lots of genetic mutations among immune checkpoints in STAD, including missense_mutation, frame_shift_del et al. Interestingly, most of immune checkpoints were associated with drug sensitivity and drug resistance. Moreover, CD274, PVR, LGALS9, ICOSLG and CD70 were associated with the overall survival, post progression survival and first progression in STAD. The univariate and multivariate analysis revealed that CD70, ICOSLG, age, pTNM stage, and radiation therapy were independent factors affecting the prognosis of STAD patients. The expression of ICOSLG and CD70 was correlated with immune cells as well as immune biomarkers, including CD8+ T cells, CD4+ T cells, macrophage, neutrophils and dendritic cells. Conclusion All in all, our study performed a comprehensive analysis of the prognostic value and immune function of immune checkpoints in STAD, and our result suggested that immune checkpoint ICOSLG and CD70 serve as prognostic biomarkers and associate with immune infiltration in STAD.

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PD-L1 Expression after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancers Is Associated with Aggressive Residual Disease, Suggesting a Potential for Immunotherapy

Cited by 11 publications

References 62 publications

Immune-Based Therapy in Triple-Negative Breast Cancer: From Molecular Biology to Clinical Practice

Immune-Based Therapy in Triple-Negative Breast Cancer: From Molecular Biology to Clinical Practice

Identification of the Prognosis Value and Potential Mechanism of Immune Checkpoints in Renal Clear Cell Carcinoma Microenvironment

Comprehensive Analysis of the Prognostic Value and Immune Function of Immune Checkpoints in Stomach Adenocarcinoma

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