Immune factors associated with the pathological and therapeutic effects of preoperative chemotherapy in patients with breast cancer

Kim, Ryungsa; Kawai, Ami; Wakisaka, Megumi; Sawada, Sayaka; Shimoyama, Mika; Yasuda, Naomi; Hidaka, Masayuki; Morita, Yukitaka; Ohtani, Shoichiro; Ito, Mitsuya; Kawasaki, K.; Kin, Takanori; Arihiro, Koji

doi:10.1016/j.tranon.2020.100927

Cited by 13 publications

(17 citation statements)

References 29 publications

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“…High platelet counts were identified as a risk factor associated with adverse outcome in numerous different tumor entities including lung cancer, breast cancer, ovarian cancer, gastric cancer, pancreas carcinoma, hepato-cellular carcinoma, colon carcinoma, renal cell carcinoma or glioblastoma to name just a few ( 21 – 28 ). Based on these robust data, and studies showing that low lymphocyte counts correlate with shorter survival time ( 29 ), the ratio between lymphocytes and platelets has been investigated and identified as a predictive marker for the disease outcome with low platelet-lymphocyte ratios (PLR) favoring a beneficial course of the disease ( 30 – 32 ). Of note, a meta-analysis including 1,340 cancer patients that were treated with an immune checkpoint inhibitor, showed a clear advantage of patients with a low PLR ( 33 ).…”

Section: Platelet-mediated Immune Escape Mechanisms In the Tumor Envimentioning

confidence: 99%

Platelet-Mediated Protection of Cancer Cells From Immune Surveillance – Possible Implications for Cancer Immunotherapy

2021

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The growing insights in the complex interactions between metastatic cancer-cells and platelets have revealed that platelet tumor cell interactions in the blood stream are an important factor supporting tumor metastasis. An increased coagulability of platelets facilitates the vascular evasion and establishment of solid tumor metastasis. Furthermore, platelets can support an immunosuppressive tumor microenvironment or shield tumor cells directly from engagement of cytotoxic lymphocytes as e.g., natural killer (NK) cells. Platelets are both in the tumor microenvironment and systemically the quantitatively most important source of TGF-β, which is a key cytokine for immunosuppression in the tumor microenvironment. If similar platelet-tumor interactions are of physiological relevance in hematological malignancies remains less well-studied. This might be important, as T- and NK cell mediated graft vs. leukemia effects (GvL) are well-documented and malignant hematological cells have a high exposure to platelets compared to solid tumors. As NK cell-based immunotherapies gain increasing attention as a therapeutic option for patients suffering from hematological and other malignancies, we review the known interactions between platelets and NK cells in the solid tumor setting and discuss how these could also apply to hematological cancers. We furthermore explore the possible implications for NK cell therapy in patients with solid tumors and patients who depend on frequent platelet transfusions. As platelets have a protective and supportive effect on cancer cells, the impact of platelet transfusion on immunotherapy and the combination of immunotherapy with platelet inhibitors needs to be evaluated.

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Section: Platelet-mediated Immune Escape Mechanisms In the Tumor Envimentioning

confidence: 99%

Platelet-Mediated Protection of Cancer Cells From Immune Surveillance – Possible Implications for Cancer Immunotherapy

2021

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“…With the exception of the direct cytotoxic/cytostatic effects of anticancer agents and ET on breast cancer cells, host defense immunity against residual tumor cells can be induced by (neo)adjuvant chemotherapy and ET. In the neoadjuvant setting, the activation of immune cells, including NK, CD4+, and CD8+ T cells, at the primary site and increases in the numbers of peripheral immune cells, including pNK and CD8+ T cells, in the blood were observed after NAC, regardless of tumor subtype [ 81 , 82 ]. These findings suggest that the coactivation of local and systemic immune responses plays an important role in the enhancement of the therapeutic effect after NAC.…”

Section: Host Defense Immunity and Breast Cancer Recurrencementioning

confidence: 99%

Clinical Perspectives in Addressing Unsolved Issues in (Neo)Adjuvant Therapy for Primary Breast Cancer

Kim¹,

Kin

2021

Cancers

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The treatment of primary breast cancer has evolved over the past 50 years based on the concept that breast cancer is a systemic disease, with the escalation of adjuvant and neoadjuvant therapies and de-escalation of breast cancer surgery. Despite the development of these therapies, recurrence with distant metastasis during the 10 years after surgical treatment is observed, albeit infrequently. Recent advances in genomic analysis based on circulating tumor cells and circulating tumor DNA have enabled the development of targeted therapies based on genetic mutations in residual tumor cells. A paradigm shift involving the application of neoadjuvant chemotherapy (NAC) has enabled the prediction of treatment response and long-term prognoses; additional adjuvant chemotherapy targeting remaining tumor cells after NAC improves survival. The activation of antitumor immunity by anticancer agents may be involved in the eradication of residual tumor cells. Elucidation of the manner in which antitumor immunity is induced by anticancer agents and unknown factors, and the overcoming of drug resistance via the targeted eradication of residual tumor cells based on genomic profiles, will inevitably lead to the achievement of 0% distant recurrence and a complete cure for primary breast cancer.

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“…Neoadjuvant chemotherapy (NAC) refers to systemic cytotoxic drug treatment before surgery or radiotherapy, and is considered as the standard treatment for patients with locally advanced or inoperable breast cancer [2,3]. Accurate evaluation of the response to neoadjuvant chemotherapy provides important information about tumor biology and prognosis and guides further therapy [4,5,6]. In addition to clinical and pathological evaluation criteria, gene expression signatures have been developed to evaluate the response to NAC [7,8].…”

Section: Introductionmentioning

confidence: 99%

A novel twelve-gene signature to evaluate neoadjuvant chemotherapy response and predict prognosis in breast cancer

Tang

Wan

Tian

et al. 2022

Preprint

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Background: Accurate evaluation of the response to neoadjuvant chemotherapy (NAC) provides important information about systemic therapies for breast cancer, which implies tumor biology, prognosis, and guide further therapy. Gene profiles overcome many limitations observed with classic histopathological variables but are complicated and expensive. Therefore, it is essential to develop a more accurate, repeatable, and economical evaluation approach for neoadjuvant chemotherapy responses. Methods: We analyzed the transcriptional profiles of chemo-resistant breast cancer cell lines and tumors of chemo-resistant breast cancer patients in the GEO25066 dataset. We preliminarily screened out common significantly differentially expressed genes and constructed a NAC response risk model using least absolute shrinkage and selection operator (LASSO) regression and univariate and multivariate analyses. The differences in prognosis, clinical features, tumor microenvironment components, and immune characteristics were compared between risk groups. The connectivity map (CMap) database was used to screen potential drugs that could reverse chemotherapy resistance in breast cancer. Results: Thirty-six genes were commonly overexpressed or downregulated in both NAC chemo-resistant tumors and cells compared to the sensitive tumors and wild-type cells. Through LASSO regression, we obtained a risk model composed of 12 genes. The risk model divided patients into high-risk and low-risk groups. Univariate and multivariate Cox regression analyses indicated that the risk score can be used as an independent prognostic factor for evaluating NAC response in breast cancer. Tumors in the high-risk and low-risk groups showed significant differences in molecular biological characteristics, tumor-infiltrating lymphocytes, and immunosuppressive molecule expression. Our results showed that the risk score was also an independent prognostic factor for breast cancer. Finally, we screened potential drugs that could reverse chemotherapy resistance in breast cancer. Conclusion: Our results suggest that the novel signature of 12 genes could be used to evaluate NAC response and predict prognosis in breast cancer.

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Immune factors associated with the pathological and therapeutic effects of preoperative chemotherapy in patients with breast cancer

Cited by 13 publications

References 29 publications

Platelet-Mediated Protection of Cancer Cells From Immune Surveillance – Possible Implications for Cancer Immunotherapy

Platelet-Mediated Protection of Cancer Cells From Immune Surveillance – Possible Implications for Cancer Immunotherapy

Clinical Perspectives in Addressing Unsolved Issues in (Neo)Adjuvant Therapy for Primary Breast Cancer

A novel twelve-gene signature to evaluate neoadjuvant chemotherapy response and predict prognosis in breast cancer

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