Dataset Information

Differential effects of CD20+ B cells and PD-L1+ immune cells on pathologic complete response and outcome: comparison between inflammatory breast cancer and locally advanced breast cancer patients.

ABSTRACT:

Purpose

This study evaluated epidemiologic and immune factors associated with pathologic complete response (pCR), breast cancer-specific survival (BCSS) and disease-free survival (DFS) outcomes in inflammatory (IBC) and locally advanced breast cancer (LABC) patients.

Methods

Tumor-infiltrating lymphocytes (TILs) and CD20⁺ B-cell frequencies (CD20⁺), and PD-L1 expression on tumor (PD-L1⁺carcinoma cells) and immune (PD-L1⁺TILs) cells were analyzed by immunohistochemistry along with clinicopathologic factors as modifiers of pCR and outcomes in 221 IBC and 162 LABC patients. Analysis included Kaplan-Meier curves and Cox proportional hazard models.

Results

IBC and LABC display similar levels of TILs, CD20⁺, and combined CD20⁺ and PD-L1⁺TILs (CD20⁺PD-L1⁺TILs), while LABC contained more PD-L1⁺TILs and PD-L1⁺ carcinoma cells. Absence of lymphovascular involvement, high TILs, PD-L1⁺ carcinoma cells, and combined CD20⁺ and PD-L1⁺ carcinoma cells correlated with pCR in IBC and LABC patients. High PD-L1⁺TILs correlated with pCR only in LABC; less lymph node involvement at diagnosis, CD20⁺ and CD20⁺PD-L1⁺TILs correlated with pCR only in IBC (P < 0.04, all comparisons). Achievement of pCR in IBC and LABC patients correlated with BCSS and DFS (P < 0.02). In multivariate analyses, pCR remained an independent prognostic factor of improved DFS in IBC and LABC patients, but of BCSS in only LABC. CD20⁺PD-L1⁺TILs remained an independent prognostic factor of improved DFS and BCSS only in IBC.

Conclusion

CD20⁺PD-L1⁺TILs are an independent prognostic biomarker of improved outcomes in IBC, but not LABC. Selecting IBC patients by CD20 and PD-L1 status could stratify patients and potentially identify those in whom activating CD20 agents and anti-PD-1/PD-L1 therapy could be explored.

SUBMITTER: Arias-Pulido H

PROVIDER: S-EPMC8603784 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

Differential effects of CD20+ B cells and PD-L1+ immune cells on pathologic complete response and outcome: comparison between inflammatory breast cancer and locally advanced breast cancer patients.

Arias-Pulido Hugo H Cimino-Mathews Ashley Marie AM Chaher Nabila N Qualls Clifford Ray CR Joste Nancy N Colpaert Cecile C Marotti Jonathan Douglas JD Chamberlin Mary Dickinson MD Foisey Maxwell Gabriel MG Prossnitz Eric Robert ER Emens Leisha Ann LA Fiering Steven S

Breast cancer research and treatment 20210920 3

<h4>Purpose</h4>This study evaluated epidemiologic and immune factors associated with pathologic complete response (pCR), breast cancer-specific survival (BCSS) and disease-free survival (DFS) outcomes in inflammatory (IBC) and locally advanced breast cancer (LABC) patients.<h4>Methods</h4>Tumor-infiltrating lymphocytes (TILs) and CD20<sup>+</sup> B-cell frequencies (CD20<sup>+</sup>), and PD-L1 expression on tumor (PD-L1<sup>+</sup>carcinoma cells) and immune (PD-L1<sup>+</sup>TILs) cells were ...[more]

PMID: 34542773

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Project description:BackgroundBreast cancer stem cells have self-renewal capability and are resistant to conventional chemotherapy. PD-L1 could promote the expression of stemness markers (OCT4 and Nanog) in breast cancer stem cells. However, the mechanisms by which PD-L1 regulates the stemness of breast cancer cells and PD-L1 is regulated in breast cancer cells are still unclear.MethodsLentivirus infection was used to construct stable cell lines. The correlation between PD-L1 and stemness markers expression was evaluated in clinical samples. Additionally, luciferase reporter assay combined with RNA-Fluorescence in situ hybridization (RNA-FISH) and RNA-binding protein immunoprecipitation (RIP) assays were used to verify the direct binding of miR-873 on PD-L1. Furthermore, flow cytometry, mammosphere formation combined with nude mouse tumor xenograft model were carried out to examine the effects of miR-873/PD-L1 axis on the stemness of breast cancer cells. Finally, MTT assay was performed to determine the effects of miR-873/PD-L1 axis on drug resistance.FindingsPD-L1 expression was positively correlated with the expression of stemness markers, and overexpression of PD-L1 contributed to chemoresistance and stemness-like properties in breast cancer cells via activating PI3K/Akt and ERK1/2 pathways. Mechanistically, miR-873 inhibited PD-L1 expression through directly binding to its 3'-untranslated region (UTR), and miR-873 attenuated the stemness and chemoresistance of breast cancer cells which was dependent on PD-L1 and the downstream PI3K/Akt and ERK1/2 signaling. Notably, the promotion of PD-L1 on the stemness and chemoresistance was enhanced by recombinant PD-1 (rPD-1), this effect was attenuated by PD-1/PD-L1 inhibitor.InterpretationmiR-873/PD-L1 regulatory axis might serve as a therapeutic target to enhance the chemo-sensitivity and eliminate the stemness of breast cancer cells. FUND: This work was supported by the National Nature Science Foundation of China, No. 81702957, China Postdoctoral Science Foundation, No. 2017M620230, the Postdoctoral Research Funding Scheme of Jiangsu Province (2017), No. 1701197B, and the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions.

Dataset Information

Differential effects of CD20+ B cells and PD-L1+ immune cells on pathologic complete response and outcome: comparison between inflammatory breast cancer and locally advanced breast cancer patients.

Purpose

Methods

Results

Conclusion

Publications

Differential effects of CD20+ B cells and PD-L1+ immune cells on pathologic complete response and outcome: comparison between inflammatory breast cancer and locally advanced breast cancer patients.

Similar Datasets

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