Triple-negative breast cancer (TNBC) escape from immune-mediated destruction was associated with immunosuppressive responses that dampened the activation of tumor-infiltrating CD8 and γδ T cells. TNBC had a higher level of programmed cell death 1-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase (IDO), compared with other breast cancer subtypes. But, clinical studies have revealed that the response rate of PD-1/PD-L1 antibody for TNBC treatment was relatively low. However, the antitumor responses of human Vγ9Vδ2 T cells or IDO inhibitor in TNBC treatment are unknown. In this study, we found that IDO1 and PD-L1 were highly expressed in TNBC patients. Analysis of the clinical samples demonstrated that Vγ9Vδ2 T cells became exhausted in triple-negative breast cancer patients. And Vγ9Vδ2 T cells combined with αPD-L1 could not further enhance their antitumor responses in vitro and in vivo. However, Vγ9Vδ2 T cells combined with IDO1 inhibitor 1-Methyl-L-tryptophan (1-MT) or Lindrostat showed substantial inhibitory effects on MDA-MB-231 tumor cells. Finally, we found that IDO1 inhibitor promoted T cell’s cytotoxicity by enhancing perforin production. These results converged to suggest the potential application of Vγ9Vδ2 T cells treated with IDO1 inhibitor for TNBC therapy.

Background: It has been a decade since the complex fractionated atrial electrograms (CFAEs) were first established following the publication of Nademanee's standards. However, the status and focus of CFAE research are unclear, as is the efficacy of additional CFAE ablation in atrial fibrillation (AF). This literature review and metaanalysis were designed to determine the status of CFAE research and the efficacy and complications of CFAE ablation alone, pulmonary vein isolation (PVI) alone and PVI plus CFAE ablation in AF. Methods: With the assistance from reference librarians and investigators trained in systematic review, we conducted a literature search of MEDLINE (via PubMed), Embase, the Cochrane Library, ScienceDirect, Wiley Blackwell and Web of Knowledge, using "complex fractionated atrial electrograms" for MeSH and keyword search. Results: The literature on CFAEs increased from 2007, mainly focusing on mapping studies, with mechanism studies increasing significantly from 2012. Fifteen trials with 1525 patients were qualified for our meta-analysis. Success rates were as follows. Overall (P b 0.001): CFAE ablation alone, 23.5-26.2%; PVI, 64.7%; PVI plus CFAE ablation, 67.0%. Single ablation: PVI, 60.4%; PVI plus CFAEs, 68.8% (OR 1.53, 95% CI 1.07-2.20, P = 0.02). Reablation: PVI, 69.0%; PVI plus CFAEs, 77.2% (OR 1.54, 95% CI 1.06-2.24, P = 0.02). Paroxysmal AF: PVI, 76.7%; PVI plus CFAEs, 79.1% (OR 1.20, 95% CI 0.79-1.81, P = 0.39). Persistent or permanent AF: PVI, 47.9%; PVI plus CFAEs, 58.7% (OR = 1.59, 95% CI 1.13-2.24, P = 0.008). Complication rates: PVI, 2.6%; PVI plus CFAEs, 3.4% (OR 1.22, 95% CI 0.58-2.57, P = 0.61). Conclusions: In the literature, CFAE mapping studies preceded mechanism studies. CFAE ablation alone is insufficient for the treatment of AF. Additional CFAE ablation after adequate PVI or PVI plus linear ablation improves the outcome of single ablation and re-ablation without increasing complications, especially in persistent or permanent AF. There are insufficient data to support a similar improvement in paroxysmal AF or inducible AF after PVI for paroxysmal AF.

Aims: Research related to type 2 diabetes mellitus (DM) and parameters of electrocardiography (ECG) was limited. Patients with and without DM (NDM) were randomly enrolled in a study to exploit the influence of DM on planar QRS and T vectors derived from the Virtual Holter process.Methods: A total of 216 (NDM) and 127 DM patients were consecutively and randomly recruited. We selected a 1-minute length of ECG, which was scheduled for analysis at 4 AM. After a series of calculating algorisms, we received the virtual planar vector parameters.Results: Patients with DM were elderly (65.61 ± 12.08 vs 59.41 ± 16.86 years, P < 0.001); higher morbidity of hypertension (76.38% vs 58.14%, P < 0.001) and coronary artery disease (44.09% vs 32.41%, P = 0.03); thicker interventricular septum (10.92 ± 1.77 vs 10.08 ± 1.96 mm, P < 0.001) and left ventricular posterior wall (9.84 ± 1.38 vs 9.39 ± 1.66 mm, P = 0.03); higher lipid levels and average heart rate (66.67 ± 12.04 vs 61.87 ± 13.36 bpm, P < 0.01); higher angle of horizontal QRS vector (HQRSA, -2.87 ± 48.48 vs -19.00 ± 40.18 degrees, P < 0.01); lower maximal magnitude of horizontal T vector (HTV, 2.33 ± 1.47 vs 2.88 ± 1.89 mm, P = 0.01) and maximal magnitude of right side T vector (2.77 ± 1.55 vs 3.27 ± 1.92 mm, P = 0.03), and no difference in angle of frontal QRS-T vector (FQRSTA, 32.77 ± 54.20 vs 28.39 ± 52.87 degrees, P = 0.74) compared with patients having NDM. After adjusting for confounding factors, DM was significantly effective on FQRSTA (regression coefficient -40.0, 95%CI -66.4 to -13.6, P < 0.01), HQRSA (regression coefficient 22.6, 95%CI 2.5 to 42.8, P = 0.03), and HTV (regression coefficient 0.9, 95%CI 0.2 to 1.7, P = 0.01). Confounding

Endocrine therapy is considered as an effective strategy for estrogen and progestogen receptor (ER and PR)-positive breast cancer (BRCA) patients, whereas resistance to these agents is the major cause of BRCA mortality in women. Immune checkpoint receptor (ICR) blockade is another approach to treat BRCA, but the response rate of this approach for non-triple-negative breast cancer (non-TNBC) is relatively low. Recently, the androgen receptor (AR) has been identified as a tumor suppressor in ER-positive BRCA; however, the relationship between the levels of androgens and ICRs on T cells in BRCA is unclear. We observed that testosterone and dihydrotestosterone (DHT) in patients with HER2 and Luminal B were significantly lower than those in healthy controls, and the expression of AR has significant correlation with overall survival (OS) advantage for Luminal B patients. Moreover, testosterone and DHT were positively correlated with the PD-1 expression on Vδ1+ T cells in HER2 and Luminal B patients. These results suggest a potential approach of combining androgens with PD-1 blockade for treating HER2 and Luminal B breast cancer.