EGFR-Specific Tyrosine Kinase Inhibitor Modifies NK Cell-Mediated Antitumoral Activity against Ovarian Cancer Cells

Mallmann-Gottschalk, Nina; Sax, Yvonne; Lang, Stephan; Brandau, Sven

doi:10.3390/ijms20194693

Cited by 27 publications

(24 citation statements)

References 49 publications

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“…Several studies have reported that EGFR-TKI targeted therapy can trigger innate and adaptive immunity by enhancing NK cell-mediated tumor cell killing, dendritic cell-mediated antigen-presenting capabilities and cytotoxic CD8 + T cell-mediated tumor lysis. 4 , 5 , 17 , 49 , 50 In the current study, we also detected the activation of NK cells, CD8 + T cells and CD4 + T cells (Supplementary Figure S7a) in peripheral blood. Chemotherapy induces immunogenic tumor cell death that increases T cell recognition and subverts the immunosuppressive state through transient lymphodepletion or stimulatory effects on immune effectors.…”

Section: Discussionsupporting

confidence: 63%

Prognostic value of the baseline circulating T cell receptor β chain diversity in advanced lung cancer

Wang

Bie

et al. 2021

OncoImmunology

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An indicator for systemic evaluation of the adaptive immune status is lacking. Peripheral blood is important in antitumour immunity, and the T-cell receptor (TCR) repertoire diversity is key for effective immunity. This study aimed to investigate changes in the circulating T cell receptor β chain (TCRB) diversity during the first few (1 ~ 4) treatment cycles and its clinical value in patients with advanced lung cancer. TCRB-enriched sequencing data combined with transcriptomic RNA sequencing data of peripheral blood leukocytes were obtained from 72 patients with advanced lung cancer before and after targeted therapy or chemotherapy. Changes in the circulating TCRB diversity during treatment and the relationship of the baseline circulating TCRB diversity with prognosis and therapeutic effects were evaluated. We found that targeted therapy or chemotherapy did not significantly affect the T lymphocyte composition or circulating TCRB diversity (3.83 vs 3.74, T-test, p = .16) in patients with advanced lung adenocarcinoma (LUAD) during the first few treatment cycles. The higher circulating TCRB diversity was linked to improved therapeutic effects (T-test, p = .00083) in LUAD patients receiving targeted therapy. Higher baseline circulating TCRB diversity was associated with better prognosis. In addition, a five-factor prognostic risk score model was built for more accurate prognosis prediction for LUAD patients. The chemotherapeutic agents for advanced lung cancer do not significantly affect adaptive immune function over the first few treatment cycles. The circulating TCRB diversity reflects the adaptive immunological repertoire and might be a convenient indicator for evaluating the adaptive immune status and prognosis.

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Section: Discussionsupporting

confidence: 63%

Prognostic value of the baseline circulating T cell receptor β chain diversity in advanced lung cancer

Wang

Bie

et al. 2021

OncoImmunology

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“…These findings suggest a role of neutrophil influx into the premetastatic niche during early-stage ovarian tumors. Results from recent studies highlight new insight about neutrophils as a "mobile fertilizer" [77] that establish the premetastatic omental niche via neutrophil extracellular traps (NETs). NETs have been found in the omentum of ovarian tumor-bearing mice before metastasis and of patients with early-stage OvCA [78].…”

Section: Neutrophilsmentioning

confidence: 99%

The Ovarian Cancer Tumor Immune Microenvironment (TIME) as Target for Therapy: A Focus on Innate Immunity Cells as Therapeutic Effectors

Baci

Bosi

Gallazzi

et al. 2020

IJMS

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Ovarian cancer (OvCA) accounts for one of the leading causes of death from gynecologic malignancy. Despite progress in therapy improvements in OvCA, most patients develop a recurrence after first-line treatments, dependent on the tumor and non-tumor complexity/heterogeneity of the neoplasm and its surrounding tumor microenvironment (TME). The TME has gained greater attention in the design of specific therapies within the new era of immunotherapy. It is now clear that the immune contexture in OvCA, here referred as tumor immune microenvironment (TIME), acts as a crucial orchestrator of OvCA progression, thus representing a necessary target for combined therapies. Currently, several advancements of antitumor immune responses in OvCA are based on the characterization of tumor-infiltrating lymphocytes, which have been shown to correlate with a significantly improved clinical outcome. Here, we reviewed the literature on selected TIME components of OvCA, such as macrophages, neutrophils, γδ T lymphocytes, and natural killer (NK) cells; these cells can have a role in either supporting or limiting OvCA, depending on the TIME stimuli. We also reviewed and discussed the major (immune)-therapeutic approaches currently employed to target and/or potentiate macrophages, neutrophils, γδ T lymphocytes, and NK cells in the OvCA context.

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“…Tumor cells pretreated with anti-epidermal growth factor receptor inhibitors showed the increased sensitivity toward NK cell-mediated antibody-dependent cellular cytotoxicity. These data implicated that combination therapies with targeted drug and immune agents would be an effective therapy ( Mallmann-Gottschalk et al, 2019 ). Further investigations of the immune-related pathways might contribute to therapeutic advances in OC.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Tumor Microenvironment Identified Prognostic Immune-Related Gene Signature in Ovarian Cancer

Zhan

2021

Front. Genet.

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BackgroundAccumulating evidence demonstrated that tumor microenvironmental cells played important roles in predicting clinical outcomes and therapeutic efficacy. We aimed to develop a reliable immune-related gene signature for predicting the prognosis of ovarian cancer (OC).MethodsSingle sample gene-set enrichment analysis (ssGSEA) of immune gene-sets was used to quantify the relative abundance of immune cell infiltration and develop high- and low-abundance immune subtypes of 308 OC samples. The presence of infiltrating stromal/immune cells in OC tissues was calculated as an estimate score. We estimated the correlation coefficients among the immune subtype, clinicopathological feature, immune score, distribution of immune cells, and tumor mutation burden (TMB). The differentially expressed immune-related genes between high- and low-abundance immune subtypes were further used to construct a gene signature of a prognostic model in OC with lasso regression analysis.ResultsThe ssGSEA analysis divided OC samples into high- and low-abundance immune subtypes based on the abundance of immune cell infiltration, which was significantly related to the estimate score and clinical characteristics. The distribution of immune cells was also significantly different between high- and low-abundance immune subtypes. The correlation analysis showed the close relationship between TMB and the estimate score. The differentially expressed immune-related genes between high- and low-abundance immune subtypes were enriched in multiple immune-related pathways. Some immune checkpoints (PDL1, PD1, and CTLA-4) were overexpressed in the high-abundance immune subtype. Furthermore, the five-immune-related-gene-signature prognostic model (CCL18, CXCL13, HLA-DOB, HLA-DPB2, and TNFRSF17)-based high-risk and low-risk groups were significantly related to OC overall survival.ConclusionImmune-related genes were the promising predictors of prognosis and survival, and the comprehensive landscape of tumor microenvironmental cells of OC has potential for therapeutic schedule monitoring.

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EGFR-Specific Tyrosine Kinase Inhibitor Modifies NK Cell-Mediated Antitumoral Activity against Ovarian Cancer Cells

Cited by 27 publications

References 49 publications

Prognostic value of the baseline circulating T cell receptor β chain diversity in advanced lung cancer

Prognostic value of the baseline circulating T cell receptor β chain diversity in advanced lung cancer

The Ovarian Cancer Tumor Immune Microenvironment (TIME) as Target for Therapy: A Focus on Innate Immunity Cells as Therapeutic Effectors

Comprehensive Analysis of Tumor Microenvironment Identified Prognostic Immune-Related Gene Signature in Ovarian Cancer

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