Circulating inflammatory cells in patients with metastatic breast cancer: Implications for treatment

Gianni, Caterina; Palleschi, Michela; Schepisi, Giuseppe; Casadei, Chiara; Bleve, Sara; Merloni, Filippo; Sirico, Marianna; Sarti, Samanta; Cecconetto, Lorenzo; Menna, Grazia; Schettini, Francesco; Giorgi, Ugo De

doi:10.3389/fonc.2022.882896

Cited by 17 publications

(14 citation statements)

References 159 publications

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“…Inflammation indexes, including SII, SIRI, NLR, MLR, and PLR, were shown as possible predictive and prognostic markers in many types of malignancies, autoimmune disorders, COVID‐19, and diabetes mellitus 10‐14 . SII and SIRI are new markers that could reflect the inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

“…Inflammation indexes, including SII, SIRI, NLR, MLR, and PLR, were shown as possible predictive and prognostic markers in many types of malignancies, autoimmune disorders, COVID-19, and diabetes mellitus. [10][11][12][13][14] SII and SIRI are new markers that could reflect the inflammatory response. SII and SIRI were first investigated in cancers, and increased levels of these indexes were related to bad outcomes.…”

Section: Discussionmentioning

confidence: 99%

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Baseline inflammation indexes and neutrophil‐to‐LDH ratio for prediction of the first mobilization failure without plerixafor‐based regimens in multiple myeloma and lymphoma patients: A single‐center retrospective study

Dirim

Tiryaki

Altın

et al. 2023

J of Clinical Apheresis

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BackgroundMany factors were identified for mobilization failure (MF) in autologous hematopoietic stem‐cell transplantation. To our knowledge, this is the first study to investigate the efficacy of baseline inflammation indexes and neutrophil‐to‐lactate dehydrogenase (LDH) ratio to predict MF in multiple myeloma (MM) and lymphoma.MethodsA total of 240 patients with lymphoma or MM hospitalized between January 2014 and June 2022 for the first stem cell mobilization were included in this retrospective single‐center study. We evaluated the impact of baseline demographic, clinical, and laboratory data (before granulocyte colony‐stimulating factor and chemotherapy implementation), including neutrophil, neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio, monocyte‐to‐lymphocyte ratio, systemic immune‐inflammation index (SII), systemic inflammatory response index (SIRI), neutrophil‐to‐C‐reactive protein, and neutrophil‐to‐LDH ratios on MF.ResultsA total of 240 patients were divided into successful (214 patients, 89.16%) and poor mobilizers (26 patients, 10.84%). Poor mobilizers had lower neutrophil, NLR, SII, and neutrophil‐to‐LDH ratios (P values were .001, .022, .001, and .001, respectively). Among these markers, only the neutrophil‐to‐LDH ratio was statistically low in both poor mobilizer MM and lymphoma patients. Receiving operator characteristic curve analysis was performed to evaluate neutrophil, SII, and neutrophil‐to‐LDH ratios for MF. Neutrophil‐to‐LDH ratio had the highest specificity (93.93%, for ≤9.904 cut‐off) compared to the other two variables. Multivariate logistic regression analysis showed that neutrophil‐to‐LDH ratio ≤ 9.904 (cut‐off) (odds ratio: 7.116, P = .001), neutrophil counts ≤3300/mm3 (cut‐off) (odds ratio: 3.248, P = .021), and lymphoma diagnosis (odds ratio: 2.674, P = .039) were independent risks for MF.ConclusionThe neutrophil‐to‐LDH ratio could be a novel marker in lymphoma and MM patients to predict the first MF. New studies should be conducted for the optimization of this index.

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Section: Discussionmentioning

confidence: 99%

“…Inflammation indexes, including SII, SIRI, NLR, MLR, and PLR, were shown as possible predictive and prognostic markers in many types of malignancies, autoimmune disorders, COVID-19, and diabetes mellitus. [10][11][12][13][14] SII and SIRI are new markers that could reflect the inflammatory response. SII and SIRI were first investigated in cancers, and increased levels of these indexes were related to bad outcomes.…”

Section: Discussionmentioning

confidence: 99%

Baseline inflammation indexes and neutrophil‐to‐LDH ratio for prediction of the first mobilization failure without plerixafor‐based regimens in multiple myeloma and lymphoma patients: A single‐center retrospective study

Dirim

Tiryaki

Altın

et al. 2023

J of Clinical Apheresis

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“…In breast cancer patients, MDSCs are enriched in peripheral circulation, which predicts advanced clinical stage, worse survival, and metastatic extension ( 24 ). Moreover, MDSCs participate in the self-seeding of circulating tumor cells leading to the local recurrence in breast cancer patients who received surgery and radiotherapy ( 25 ), and MDSCs contribute to the immunosuppressive tumor microenvironment and hinder the therapeutic efficacy.…”

Section: Discussionmentioning

confidence: 99%

Combining all-trans retinoid acid treatment targeting myeloid-derived suppressive cells with cryo-thermal therapy enhances antitumor immunity in breast cancer

et al. 2022

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Targeting myeloid-derived suppressive cells (MDSCs) has been considered a potential strategy in tumor therapy. However, a single drug targeting MDSCs remains a challenge in the clinic. An increasing number of studies have shown that combination agents targeting MDSCs and immunotherapy may provide exciting new insights and avenues to explore in tumor therapy. In our previous study, a novel cryo-thermal therapy was developed for metastatic tumors that systematically activate innate and adaptive immunity. Moreover, cryo-thermal therapy was shown to dramatically decrease the levels of MDSCs and induce their differentiation toward potent antigen-presenting cells. However, the therapeutic effects of cryo-thermal therapy on the 4T1 mouse breast cancer model were still not satisfactory because of the high level of MDSCs before and after treatment. Therefore, in this study, we combined cryo-thermal therapy with all-trans retinoid acid (ATRA), a small molecule drug that can induce the inflammatory differentiation of MDSCs. We found that combination therapy notably upregulated the long-term survival rate of mice. Mechanically, combination therapy promoted the phenotype and functional maturation of MDSCs, efficiently decreasing suppressive molecule expression and inhibiting glutamine and fatty acid metabolism. Moreover, MDSCs at an early stage after combination therapy significantly decreased the proportions of Th2 and Treg subsets, which eventually resulted in Th1-dominant CD4+ T-cell differentiation, as well as enhanced cytotoxicity of CD8+ T cells and natural killer cells at the late stage. This study suggests a potential therapeutic strategy for combination ATRA treatment targeting MDSCs with cryo-thermal therapy to overcome the resistance of MDSC-induced immunosuppression in the clinic.

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“…The use of programmed PD-L1 and tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers is well-recognized and associated with response to immunotherapy, although the latter biomarker is related to pathological specimens often found in the primary tumor site [170,171]. Several biomarkers of immunological state such as circulating tumor cells, circulating immunity cells and inflammatory indexes have been investigated as predictive and prognostic biomarkers [172][173][174][175].…”

Section: Impact Of Biomarkersmentioning

confidence: 99%

Current State and Future Challenges for PI3K Inhibitors in Cancer Therapy

Sirico

D’Angelo

Gianni

et al. 2023

Cancers

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The phosphoinositide 3 kinase (PI3K)-protein kinase B (PKB/AKT)-mammalian target of the rapamycin (mTOR) axis is a key signal transduction system that links oncogenes and multiple receptor classes which are involved in many essential cellular functions. Aberrant PI3K signalling is one of the most commonly mutated pathways in cancer. Consequently, more than 40 compounds targeting key components of this signalling network have been tested in clinical trials among various types of cancer. As the oncogenic activation of the PI3K/AKT/mTOR pathway often occurs alongside mutations in other signalling networks, combination therapy should be considered. In this review, we highlight recent advances in the knowledge of the PI3K pathway and discuss the current state and future challenges of targeting this pathway in clinical practice.

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Circulating inflammatory cells in patients with metastatic breast cancer: Implications for treatment

Cited by 17 publications

References 159 publications

Baseline inflammation indexes and neutrophil‐to‐LDH ratio for prediction of the first mobilization failure without plerixafor‐based regimens in multiple myeloma and lymphoma patients: A single‐center retrospective study

Baseline inflammation indexes and neutrophil‐to‐LDH ratio for prediction of the first mobilization failure without plerixafor‐based regimens in multiple myeloma and lymphoma patients: A single‐center retrospective study

Combining all-trans retinoid acid treatment targeting myeloid-derived suppressive cells with cryo-thermal therapy enhances antitumor immunity in breast cancer

Current State and Future Challenges for PI3K Inhibitors in Cancer Therapy

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