Correction : Control of PD-L1 expression by miR-140/142/340/383 and oncogenic activation of the OCT4-miR-18a pathway in cervical cancer.

This research was supported by a grant from the Department of Women’s Health Educational System, JSPS Grant-in-Aid for Scientific Research (C) (15K10697 and 16K11123) and the Science and Technology Planning Project of Guangdong Province, China (2014A020212124). We thank Dr. Zhujie Xu for experimental assistance. The authors declare that they have no conflict of interest.Peer reviewedPublisher PD

Locally advanced rectal cancer with dMMR/MSI-H may be excused from surgery after neoadjuvant anti-PD-1 monotherapy: a multiple-center, cohort study

ObjectiveExamine patients with locally advanced rectal cancer (LARC) with deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) who received neoadjuvant immunotherapy (nIT), and compare the outcomes of those who chose a watch-and-wait (WW) approach after achieving clinical complete response (cCR) or near-cCR with those who underwent surgery and were confirmed as pathological complete response (pCR).MethodsLARC patients with dMMR/MSI-H who received nIT were retrospectively examined. The endpoints were 2-year overall survival (OS), 2-year disease-free survival (DFS), local recurrence (LR), and distant metastasis (DM). The efficacy of programmed cell death protein-1 (PD-1) inhibitor, immune-related adverse events (irAEs), surgery-related adverse events (srAEs), and enterostomy were also recorded.ResultsTwenty patients who received a PD-1 inhibitor as initial nIT were examined. Eighteen patients (90%) achieved complete response (CR) after a median of 7 nIT cycles, including 11 with pCR after surgery (pCR group), and 7 chose a WW strategy after evaluation as cCR or near-cCR (WW group). Both groups had median follow-up times of 25.0 months. Neither group had a case of LR or DM, and the 2-year DFS and OS in each group was 100%. The two groups had similar incidences of irAEs (P=0.627). In the pCR group, however, 2 patients (18.2%) had permanent colostomy, 3 (27.3%) had temporary ileostomy, and 2 (18.2%) had srAEs.ConclusionNeoadjuvant PD-1 blockade had high efficacy and led to a high rate of CR in LARC patients with dMMR/MSI-H. A WW strategy appears to be a safe and reliable option for these patients who achieve cCR or near-cCR after nIT

Control of PD-L1 expression by miR-140/142/340/383 and oncogenic activation of the OCT4–miR-18a pathway in cervical cancer

PD-L1, a key inhibitory immune receptor, has crucial functions in cancer immune evasion, but whether PD-L1 promotes the malignant properties of cervical cancer (CC) cells and the mechanism by which PD-L1 is regulated in CC remains unclear. We report that PD-L1 is overexpressed in CC, and shRNA-mediated PD-L1 depletion suppresses the proliferation, invasion, and tumorigenesis of CC cells. Loss of miR-140/142/340/383 contributes to PD-L1 upregulation. miR-18a enhances PD-L1 levels by targeting PTEN, WNK2 (ERK1/2 pathway inhibitor), and SOX6 (Wnt/β-catenin pathway inhibitor and p53 pathway activator) to activate the PI3K/AKT, MEK/ERK, and Wnt/β-catenin pathways and inhibit the p53 pathway, and miR-18a also directly suppresses the expression of the tumor suppressors BTG3 and RBSP3 (CTDSPL). miR-18a overexpression in CC cells is triggered by OCT4 overexpression. Our data implicate PD-L1 as a novel oncoprotein and indicate that miR-140/142/340/383 and miR-18a are key upstream regulators of PD-L1 and potential targets for CC treatment

The effects of oxaliplatin-based adjuvant chemotherapy in high-risk stage II colon cancer with mismatch repair-deficient: a retrospective study

Abstract Background For high-risk stageIImismatch repair deficient (dMMR) colon cancers, the benefit of adjuvant chemotherapy remains debatable. The principal aim of this study was to evaluate the prognostic value of high-risk factors and the effect of oxaliplatin-based adjuvant chemotherapy among dMMR stageIIcolon cancers. Methods Patients with stage II dMMR colon cancers diagnosed between June 2011 and May 2018 were enrolled in the study. Clinicopathological characteristics, treatment, and follow-up data were retrospectively collected. The high-risk group was defined as having one of the following factors: pT4 disease, fewer than twelve lymph nodes harvested (< 12 LNs), poorly differentiated histology, perineural invasion (PNI), lymphatic vascular invasion (LVI), or elevated preoperative carcinoembryonic antigen (CEA). The low-risk group did not have any risk factors above. Factors associated with disease-free survival (DFS) were included in univariate and multivariate Cox analyses. Results We collected a total of 262 consecutive patients with stage II dMMR colon cancer. 179 patients (68.3%) have at least one high-risk factor. With a median follow-up of 50.1 months, the low-risk group was associated with a tended to have a better 3-year DFS than the high-risk group (96.4% vs 89.4%; P = 0.056). Both elevated preoperative CEA (HR 2.93; 95% CI 1.26–6.82; P = 0.013) and pT4 disease (HR 2.58; 95% CI 1.06–6.25; P = 0.037) were independent risk factors of recurrence. Then, the 3-year DFS was 92.6% for the surgery alone group and 88.1% for the adjuvant chemotherapy group (HR 1.64; 95% CI 0.67–4.02; P = 0.280). Furthermore, no survival benefit from oxaliplatin-based adjuvant chemotherapy was observed in the high-risk group and in the subgroups with pT4 disease or < 12 LNs. Conclusions These data suggests that not all high-risk factors have a similar impact on stage II dMMR colon cancers. Elevated preoperative CEA and pT4 tumor stage are associated with increased recurrence risk. However, oxaliplatin-based adjuvant chemotherapy shows no survival benefits in stage II dMMR colon cancers, either with or without high-risk factors

Additional file 1 of The effects of oxaliplatin-based adjuvant chemotherapy in high-risk stage II colon cancer with mismatch repair-deficient: a retrospective study

Additional file 1: Fig S1. Flow of study