Overexpression of PD-1 and CD39 in tumor-infiltrating lymphocytes compared with peripheral blood lymphocytes in triple-negative breast cancer

Zahran, Asmaa M; Rayan, Amal; Zahran, Zeinab Albadry M.; Mohamed, W. S.; Mohamed, Dalia O.; Abdelrahim, Mahmoud; El‐Badawy, Omnia

doi:10.1371/journal.pone.0262650

Cited by 13 publications

(6 citation statements)

References 46 publications

(46 reference statements)

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“…The suppression of tumor growth attained through the combined treatment was associated with an increased systemic proportion of T cells and increased PD-1 expression on CD8 T cells in the spleen. Notably, these data align with clinical observations, demonstrating an increased PD-1 expression on infiltrating immune cells, in particular in early TNBC ( 54 ) and untreated HR-pos. BCs ( 55 , 56 ).…”

Section: Discussionsupporting

confidence: 88%

Neoadjuvant radiotherapy in ER+, HER2+, and triple-negative -specific breast cancer based humanized tumor mice enhances anti-PD-L1 treatment efficacy

Bruss,

Albert,

Seitz

et al. 2024

Front. Immunol.

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Pre-operative radiation therapy is not currently integrated into the treatment protocols for breast cancer. However, transforming immunological “cold” breast cancers by neoadjuvant irradiation into their “hot” variants is supposed to elicit an endogenous tumor immune defense and, thus, enhance immunotherapy efficiency. We investigated cellular and immunological effects of sub-lethal, neoadjuvant irradiation of ER pos., HER2 pos., and triple-negative breast cancer subtypes in-vitro and in-vivo in humanized tumor mice (HTM). This mouse model is characterized by a human-like immune system and therefore facilitates detailed analysis of the mechanisms and efficiency of neoadjuvant, irradiation-induced “in-situ vaccination”, especially in the context of concurrently applied checkpoint therapy. Similar to clinical appearances, we observed a gradually increased immunogenicity from the luminal over the HER2-pos. to the triple negative subtype in HTM indicated by an increasing immune cell infiltration into the tumor tissue. Anti-PD-L1 therapy divided the HER2-pos. and triple negative HTM groups into responder and non-responder, while the luminal HTMs were basically irresponsive. Irradiation alone was effective in the HER2-pos. and luminal subtype-specific HTM and was supportive for overcoming irresponsiveness to single anti-PD-L1 treatment. The treatment success correlated with a significantly increased T cell proportion and PD-1 expression in the spleen. In all subtype-specific HTM combination therapy proved most effective in diminishing tumor growth, enhancing the immune response, and converted non-responder into responder during anti-PD-L1 therapy. In HTM, neoadjuvant irradiation reinforced anti-PD-L1 checkpoint treatment of breast cancer in a subtype –specific manner. According to the “bench to bedside” principle, this study offers a vital foundation for clinical translating the use of neoadjuvant irradiation in the context of checkpoint therapy.

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Section: Discussionsupporting

confidence: 88%

Neoadjuvant radiotherapy in ER+, HER2+, and triple-negative -specific breast cancer based humanized tumor mice enhances anti-PD-L1 treatment efficacy

Bruss,

Albert,

Seitz

et al. 2024

Front. Immunol.

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“…In developed countries, breast cancer is the number one cancer in women. The incidence of breast cancer in China is showing a trend of younger age [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Bioinformatics Method Was Used to Analyze the Highly Expressed Gene FAM83A of Breast Cancer in Young Women

Tang

Wang

et al. 2022

Applied Bionics and Biomechanics

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Objectives. Preliminary analysis of breast cancer related to unknown functional gene FAM83A through bioinformatics knowledge to inform further experimental studies. Select high expression genes for breast cancer and use bioinformatics methods to predict the biological function of FAM83A. Methods. Genes with significant differences in expression between breast tumors and normal breast tissue libraries were selected from CGAP’s SAGE Digital Gene Expression Displayer (DGED) database. An unknown functional gene, FAM83A, which is highly expressed in breast cancer, was screened. We performed an analysis of the gene structure, subcellular localization, physicochemical properties of the encoding products, functional sites, protein structure, and functional domains. Results. Through SAGE DGED, a total of 185 genes with expression differences were found. The structure and function of FAM83A have ideal predictions, and it is generally determined that this gene encodes a nuclear protein with a nucleoprotein. The active site of PLDc and the functional domain of DUF1669 can be involved in signal transduction and gene expression regulation in tumorigenesis and metastasis. Digital gene representation of the Tumor Genome Project Data Library was used to select differentially expressed genes in breast cancer tissue and breast benign tumor tissue. Conclusion. Studies show that FAM83A is a potential research target associated with tumorigenesis and metastasis. Initial tests confirmed the expression of this gene. Lay a solid foundation for further research learning. FAM83A is a highly expressed gene in breast cancer and can serve as a target for studying molecular mechanisms in breast cancer.

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“…Tumor-infiltrating immune cells may reflect the local immune response in the tumor microenvironment, and peripheral circulating immune cells are key indicators for assessing overall immune status in vivo . To a certain extent, the abundance of intratumoral tumor-reactive T cells is proportional to the number of tumor-reactive T cell clones in the peripheral blood ( 20 , 21 ). Hence, circulating immune cells could provide valuable information about immune function in patients with NPC ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

Abnormal variation and prognostic significance of circulating immune cells in patients with nasopharyngeal carcinoma treated with chemoradiotherapy: a prospective cohort study

Huang,

Ding,

Huang

et al. 2023

Transl Cancer Res

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Background Circulating immune cells are associated with tumor development and poor prognosis in multiple solid tumors. However, the circulating immune-cell profile of nasopharyngeal carcinoma (NPC) remains largely unknown. Therefore, we aimed to determine the changes in immune status and the prognostic significance of circulating immune cells before and after chemoradiotherapy (CRT) in patients, which can provide clinicians with valuable insights to optimize treatment strategies, monitor immune function, and personalize interventions, ultimately improving patient outcomes. Methods Circulating immune cells before and after CRT in 77 patients with NPC and in 30 healthy controls were measured with flow cytometry. A thorough follow-up was conducted to assess prognosis outcomes, including local failure-free rate (LFFR), distant failure-free rate (DFFR), disease-free survival (DFS), and overall survival (OS). The differences of the subpopulation distribution in the two groups were determined by t -tests or Mann-Whitney tests. The paired t -test or Wilcoxon matched-pairs signed rank test was used to compare differences in lymphocyte subsets before and after CRT. The prognostic significance of lymphocyte subsets was evaluated by Kaplan-Meier analysis and Cox proportional hazards model. Results Compared with the control group, the NPC group showed significant decreases in the proportions of CD3 + cells, CD4 + T cells, CD8 + CD28 + T cells, and CD19 + B cells as well as the CD4 + :CD8 + ratio (P<0.05) but a significant increase in the proportion of natural killer (NK) cells (P<0.05). After CRT, the proportions of CD4 + cells, CD8 + CD28 + T cells, and CD19 + B cells as well as the CD4 + :CD8 + ratio were markedly decreased (P<0.05), while the proportions of CD8 + T cells and NK cells were significantly increased (P<0.05). Multivariate analysis showed that a lower percentage of CD19 + B cells [hazard ratio (HR) 6.550, 95% CI: 1.661–25.831; P=0.007] and a positive test for Epstein-Barr virus (EBV) DNA (HR 0.261, 95% CI: 0.074–0.926; P=0.038) before treatment independently predicted worse 5-year OS (P<0.05). Conclusions The disproportion of circulating immune cells was observed in patients with NPC before treatment. CRT further aggravated immune dysfunction. Notably, a lower percentage of CD19 + B cells and EBV DNA-positive status before treatment were independent predictors of a worse prognosis. Thus, the measurement of circulating immune cells ...

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Overexpression of PD-1 and CD39 in tumor-infiltrating lymphocytes compared with peripheral blood lymphocytes in triple-negative breast cancer

Cited by 13 publications

References 46 publications

Neoadjuvant radiotherapy in ER+, HER2+, and triple-negative -specific breast cancer based humanized tumor mice enhances anti-PD-L1 treatment efficacy

Neoadjuvant radiotherapy in ER+, HER2+, and triple-negative -specific breast cancer based humanized tumor mice enhances anti-PD-L1 treatment efficacy

Bioinformatics Method Was Used to Analyze the Highly Expressed Gene FAM83A of Breast Cancer in Young Women

Abnormal variation and prognostic significance of circulating immune cells in patients with nasopharyngeal carcinoma treated with chemoradiotherapy: a prospective cohort study

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