An Immunoscore Using PD-L1, CD68, and Tumor-infiltrating Lymphocytes (TILs) to Predict Response to Neoadjuvant Chemotherapy in Invasive Breast Cancer

McLemore, Lauren E.; Janakiram, Murali; Albanese, Joseph; Shapiro, Nella; Lo, Yungtai; Zang, Xingxing; Fineberg, Susan

doi:10.1097/pai.0000000000000485

Cited by 24 publications

(15 citation statements)

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“…Out of all different subtypes of BC, TNBC and HER2 + BCs are identified to have a significant association with the immune surveillance of the host [19,22]. These studies also highlight the significance of immunomodulation, the number of tumor-infiltrating lymphocytes, and the expression of programmed death-ligand (PD-L1) to the disease prognosis and treatment outcome pertaining to human BC [16,[22][23][24]. All these findings emphasize the importance of further investigating the applicability of immunotherapy for HER2 + BC.…”

Section: Introductionmentioning

confidence: 94%

“…Several studies evaluate the importance of PD-1/PD-L1 expression on tumor cells and/or immune cells and the presence of TILs and Tregs in the tumor microenvironment in predicting response to treatment pertaining to BC [3,104,108,113,114]. Specifically, blocking immune evasion and attracting more TILs and fewer Tregs (reactivating immunogenicity of BC) to the tumor microenvironment can improve the OS of BC patients [19,23,[115][116][117][118][119]. Sixteen percent of HER2 + subtypes are lymphocyte predominant (> 50-60% of TILs present) and are associated with improved outcome (EFS: event-free survival, OS) with many treatment modalities [19,[120][121][122][123][124].…”

Section: Pd-1/pd-l1 and Her2 Crosstalk In Breast Cancermentioning

confidence: 99%

“…Moreover, based on 6 different studies, in [130], the authors highlight that PD-L1 expression in both tumor cells and immune cells of the host can contribute to the overall response to treatment. Hence, the evaluation of an overall expression in both these cells is recommended as a predictive biomarker [23,[115][116][117][118][119].…”

Section: Pd-1/pd-l1 and Her2 Crosstalk In Breast Cancermentioning

confidence: 99%

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Crosstalk between HER2 and PD-1/PD-L1 in Breast Cancer: From Clinical Applications to Mathematical Models

Padmanabhan

Kheraldine

Meskin

et al. 2020

Cancers

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Breast cancer is one of the major causes of mortality in women worldwide. The most aggressive breast cancer subtypes are human epidermal growth factor receptor-positive (HER2+) and triple-negative breast cancers. Therapies targeting HER2 receptors have significantly improved HER2+ breast cancer patient outcomes. However, several recent studies have pointed out the deficiency of existing treatment protocols in combatting disease relapse and improving response rates to treatment. Overriding the inherent actions of the immune system to detect and annihilate cancer via the immune checkpoint pathways is one of the important hallmarks of cancer. Thus, restoration of these pathways by various means of immunomodulation has shown beneficial effects in the management of various types of cancers, including breast. We herein review the recent progress in the management of HER2+ breast cancer via HER2-targeted therapies, and its association with the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) axis. In order to link research in the areas of medicine and mathematics and point out specific opportunities for providing efficient theoretical analysis related to HER2+ breast cancer management, we also review mathematical models pertaining to the dynamics of HER2+ breast cancer and immune checkpoint inhibitors.

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Section: Introductionmentioning

confidence: 94%

Section: Pd-1/pd-l1 and Her2 Crosstalk In Breast Cancermentioning

confidence: 99%

Section: Pd-1/pd-l1 and Her2 Crosstalk In Breast Cancermentioning

confidence: 99%

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Crosstalk between HER2 and PD-1/PD-L1 in Breast Cancer: From Clinical Applications to Mathematical Models

Padmanabhan

Kheraldine

Meskin

et al. 2020

Cancers

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“…65 This system has been used extensively in hepatocellular carcinoma, melanoma, colorectal, high-grade serous ovarian, invasive breast and gastric cancer. [66][67][68][69][70][71][72][73][74][75][76] By routinely calculating an Immunoscore at the time of diagnosis prior to treatment with immune therapy, we may find that the Immunoscore can predict responses to checkpoint inhibition.…”

Section: Immunoscore In Non-cns Malignanciesmentioning

confidence: 99%

Biomarkers for immunotherapy for treatment of glioblastoma

Lynes

Nwankwo

Sur

et al. 2020

J Immunother Cancer

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Immunotherapy is a promising new therapeutic field that has demonstrated significant benefits in many solid-tumor malignancies, such as metastatic melanoma and non-small cell lung cancer. However, only a subset of these patients responds to treatment. Glioblastoma (GBM) is the most common malignant primary brain tumor with a poor prognosis of 14.6 months and few treatment advancements over the last 10 years. There are many clinical trials testing immune therapies in GBM, but patient responses in these studies have been highly variable and a definitive benefit has yet to be identified. Biomarkers are used to quantify normal physiology and physiological response to therapies. When extensively characterized and vigorously validated, they have the potential to delineate responders from non-responders for patients treated with immunotherapy in malignancies outside of the central nervous system (CNS) as well as GBM. Due to the challenges of current modalities of radiographic diagnosis and disease monitoring, identification of new predictive and prognostic biomarkers to gauge response to immune therapy for patients with GBM will be critical in the precise treatment of this highly heterogenous disease. This review will explore the current and future strategies for the identification of potential biomarkers in the field of immunotherapy for GBM, as well as highlight major challenges of adapting immune therapy for CNS malignancies.

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“…FANG LIU 1,2,6* , BENOÎT SANSAS 3* , XAVIER PRÉVILLE 3,7 , ROMAIN GINESTE 1,2,8 , JIALEI WANG 4,5 , HUI YU 4,5 , XIA MENG 1,2 , ROMAIN MICOL 3,9 and LUC BARRAUD 3 studies demonstrated that the immune status of the patient is crucial, as it may affect treatment outcome (7,8). In addition, recent studies demonstrated that chemotherapy clearly affects immune effectors, such as PD-L1 expression and/or tumor-infiltrating lymphocyte (TIL) infiltration (9,10).…”

Section: Elevated Il-6/il-1ra Ratio As a Prognostic Biomarker Of Poormentioning

confidence: 99%

Elevated IL‑6/IL‑1Ra ratio as a prognostic biomarker of poor chemotherapy efficacy in Chinese patients with metastatic NSCLC, validated in a Caucasian patient cohort

Liu¹,

Sansas

Préville

et al. 2018

mol clin onc

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The treatment options for advanced (stage IV) non-small cell lung cancer (NSCLC) at diagnosis remain disappointing. The development of immunotherapeutic drugs may represent a promising alternative approach to the treatment of late-stage cancer at diagnosis. These current paradigms in cancer treatment highlight the need for new biomarkers related to the immune status of the patients and/or the tumor microenvironment, for immune as well as chemotherapeutic treatment options. The aim of the present study was to analyze soluble immune factors in patients with lung cancer treated with chemotherapy to identify prognostic biomarkers. For this purpose, the data obtained from two cohorts of patients from different clinical trials were analyzed: A Chinese patient cohort to identify potential prognostic biomarkers, and a validation cohort comprising patients with a similar clinical stage from a clinical trial in Europe. Analyses of soluble markers for inflammation and immune status were performed by standard assays and multiplex Luminex assays. Differences in overall survival (OS) and progression-free survival (PFS) were evaluated with the log-rank test and robustness was evaluated with the resampling approach. In the Chinese cohort, four prognostic biomarkers of poor response to chemotherapy were identified, which had a significant impact on OS and PFS. It was confirmed in the Caucasian validation cohort that an increased value of the interleukin (IL)-6/IL-1Ra cytokine ratio at inclusion was correlated with significantly shorter OS and PFS, whereas no other biomarkers were found to be significant. The IL-6/IL-1Ra ratio reflects the imbalance between pro-and anti-inflammatory status in the plasma of patients and may be associated with tumor inflammatory status and the therapeutic outcome. The present study highlights the identification of the IL-6/IL-1Ra ratio as a biomarker of poor prognosis in terms of response to chemotherapy in two independent clinical studies.

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An Immunoscore Using PD-L1, CD68, and Tumor-infiltrating Lymphocytes (TILs) to Predict Response to Neoadjuvant Chemotherapy in Invasive Breast Cancer

Cited by 24 publications

References 30 publications

Crosstalk between HER2 and PD-1/PD-L1 in Breast Cancer: From Clinical Applications to Mathematical Models

Crosstalk between HER2 and PD-1/PD-L1 in Breast Cancer: From Clinical Applications to Mathematical Models

Biomarkers for immunotherapy for treatment of glioblastoma

Elevated IL‑6/IL‑1Ra ratio as a prognostic biomarker of poor chemotherapy efficacy in Chinese patients with metastatic NSCLC, validated in a Caucasian patient cohort

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