T cell-inflamed phenotype and increased Foxp3 expression in infiltrating T-cells of mismatch-repair deficient endometrial cancers

Asaka, Shiho; Yen, Ting Tai; Wang, Tian Li; Shih, Ie Ming; Gaillard, Stéphanie

doi:10.1038/s41379-018-0172-x

Cited by 30 publications

(28 citation statements)

References 51 publications

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“…In general, CD8 + T lymphocytes play a vital role in attacking tumour cells via cytotoxicity. A lack of CD3 + or CD8 + T lymphocytes in EC was usually believed to be related to poor prognosis [33]. In light of the uncertain mechanisms and some of the bidirectional indicators above, the combination of NLR, PLR and MLR may be a superior prognostic factor of EC that reflects the actual status of tumour-associated immunoreaction.…”

Section: Discussionmentioning

confidence: 99%

Combination of preoperative neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and monocyte-lymphocyte ratio: a superior prognostic factor of endometrial cancer

Cong

Kong

et al. 2020

BMC Cancer

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Background: The preoperative peripheral blood neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and monocyte-lymphocyte ratio (MLR) have been reported to be associated with the prognosis of various cancers but are always discussed separately. The aim of this study is to bring the combination of NLR, PLR and MLR into the prognostic assessment system of endometrial cancer (EC) and establish a nomogram to provide an objective prediction model for clinical decisions. Methods: A total of 1111 patients with EC who had accepted surgical treatment during 2013-2017 were involved in the analysis. Their NLR, PLR, and MLR levels were obtained from a routine blood examination within 2 weeks before operation. Receiver operating characteristic curve (ROC) analysis was performed to determine optimal cutoffs. Chi-square tests analysed the associations of the ratios with other clinicopathological variables. The prognostic value was indicated by overall survival (OS) via Cox proportional hazards models and Kaplan-Meier analysis. R software was used to establish the nomogram based on the combination of NLR, PLR, MLR and other clinicopathological factors. Results: The median follow-up period was 40 months, and the median age was 56. The enrolled patients were stratified by cutoffs of 2.14 for NLR, 131.82 for PLR and 0.22 for MLR. Multivariate analyses demonstrated that high NLR over 2.14 (HR = 2.71, 95%CI = 1.83-4.02, P<0.001), high PLR over 131.82 (HR = 2.75, 95%CI = 1.90-3.97, P<0.001), and high MLR over 0.22 (HR = 1.72, 95%CI = 1.20-2.45, P = 0.003) were significantly associated with worse OS. The combined indicator, high NLR + high PLR + high MLR (HR = 4.34, 95%CI = 2.54-7.42, P<0.001), showed the highest prognostic value. The Harrell's concordance index of the nomogram was 0.847 (95% CI = 0.804-0.890), showing good discrimination and calibration of this model.

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Section: Discussionmentioning

confidence: 99%

Combination of preoperative neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and monocyte-lymphocyte ratio: a superior prognostic factor of endometrial cancer

Cong

Kong

et al. 2020

BMC Cancer

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“…Indeed, there is an association between pre-treatment Foxp3+ T-reg infiltration, followed by a subsequent increase in TILs 3 weeks into treatment in melanoma biopsies which was associated with response to the CTLA4-targeting antibody ipilimumab (48). Whether this is a causal relationship, or a bystander effect of enhanced inflammation remains to be established, as infiltration of the TME with T-regs usually coexists with an inflammatory response that also includes CD8 + T cells, macrophages and granulocytes (49,50). Conversely, T-regs and T effector cells express similar levels of PD-1 (51), and anti-PD-1 antibodies do not deplete cells expressing the target, but the Fc portion can modulate myeloid cell activity (37).…”

Section: T Cellsmentioning

confidence: 99%

Sensitizing the Tumor Microenvironment to Immune Checkpoint Therapy

et al. 2020

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Immune checkpoint blockade (ICB) has revolutionized cancer treatment, providing remarkable clinical responses in some patients. However, the majority of patients do not respond. It is therefore crucial both to identify predictive biomarkers of response and to increase the response rates to immune checkpoint therapy. In this review we explore the current literature about the predictive characteristics of the tumor microenvironment and discuss therapeutic approaches that aim to change this toward a milieu that is conducive to response. We propose a personalized biomarker-based adaptive approach to immunotherapy, whereby a sensitizing therapy is tailored to the patient's specific tumor microenvironment, followed by on-treatment verification of a change in the targeted biomarker, followed by immune checkpoint therapy. By incorporating detailed knowledge of the immunological tumor microenvironment, we may be able to sensitize currently non-responsive tumors to respond to immune checkpoint therapy.

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“…[11] reported that high levels of TILs and peritumoral lymphocyte infiltration could predict microsatellite instability (MSI) in EC with 85 and 46% sensitivity and specificity, respectively. Similarly, Asaka et al [12] reported that EC patients with mismatch repair deficiency show higher levels of CD8 + T cells, Tregs, and PD-1 + immune cells, while Workel et al [13] found a correlation between elevated CD8 + PD-1 + lymphocytes and better EC prognosis. Other studies have shown that high numbers of Treg cells correlate with poor prognosis of patients with EC [14].…”

Section: Discussionmentioning

confidence: 95%