Reversal of the immunosuppressive tumor microenvironment via platinum-based neoadjuvant chemotherapy in cervical cancer

Background Immunotherapy favors patients with tumors;however,only 3-26.3%of patients with cervical cancer benefit from single-agent immune checkpoint inhibitors.Combined immunotherapy and chemotherapy has been explored against tumor;however,the combination remains controversial.This study aimed to investigate the tumor immune microenvironment(TIME)and the effects of platinum-based neoadjuvant chemotherapy(NACT)in cervical cancer to identify the clinical value of combining chemotherapy with immunotherapy.Methods Multiplex immunohistochemistry(IHC)with 11 markers(cluster of differentiation[CD]3,CD8,CD4,CD11c,CD68,forkhead box P3[Foxp3],programmed cell death 1[PD-1],programmed cell death 1 ligand 1[PD-L1],indoleamine 2,3-dioxygenase[IDO],cyclin-dependent kinase inhibitor 2A[p16],and cytokeratin[CK])was performed to evaluate TIME from 108 matched pre-and post-NACT cervical cancer samples.The mechanism of antitumor immunity triggered by NACT was explored using RNA sequencing(RNA-seq)from four paired samples and subsequently verified in 41 samples using IHC.Results The infiltration rate of the CD8^(+)T cells in treatment-naive cervical cancer was 0.73%,and those of Foxp3^(+)regulatory T cells(Tregs)and IDO^(+)cells were 0.87%and 17.15%,respectively.Moreover,immunoreactive T cells,dendritic cells,and macrophages were more in the stromal than the intratumor region.NACT increased dendritic,CD3^(+)T,CD8^(+)T,and CD4^(+)T cells and decreased Tregs.The aforementioned alterations occurred predominantly in the stromal region and were primarily in responders.Non-responders primarily showed decreased Tregs and no increase in CD8^(+)T or dendritic cell infiltration.Furthermore,dendritic cells interacted more closely with CD3^(+)T cells after NACT,an effect primarily observed in responders.RNA-seq data revealed activation of the antigen receptor-mediated signaling pathway and upregulation of major histocompatibility complex(MHC)I and MHC II after chemotherapy,validated using IHC.Conclusions NACT can reduce Tregs,and when tumor cells are effectively killed,antigen presentation is enhanced,subsequently activating antitumor immunity finitely.Our study provides the molecular characteristics and theoretical basis for the simultaneous or sequential combination of platinum-based NACT and immunotherapy for cervical cancer.

Propensity score-matched study and meta-analysis of cumulative outcomes of day 2/3 versus day 5/6 embryo transfers

The superiority of the cumulative outcomes of day 5/6 embryo transfer to those of day 2/3 embryo transfer in infertile couples has been debated. This retrospective study included data collected from 1051 patients from July 2011 to June 2014. Multiple maternal baseline covariates were subjected to propensity score matching analysis, and each day 5/6 group woman was matched to one day 2/3 group woman. A systematic meta-analysis was conducted to vaUdate the results. After matching was completed, 217 patients on the day 2/3 group were matched with those on the day 5/6 group, and no significant differences in the baseline characteristics were observed between the two groups. The cumulative pregnancy rate （57.14% vs. 53.46%, OR 1.16, 95% CI 0.79-1.70） and cumulative live birth rate （53.00% vs. 49.77%, OR 1.14, 95% CI 0.78-1.66） of day 5/6 embryo transfers were higher than those of day 2/3 embryo transfers, but this difference was not significant. The mean cycles per live birth and mean days per live birth in the day 5/6 group were significantly lower than those in the day 2/3 group. This study demonstrated that day 5/6 embryo transfer is a more cost-effective and time-efficient policy than day 2/3 embryo transfer to produce a live baby.

Differential immune responses in pregnant patients recovered from COYID-19

Pregnant women are generally more susceptible to viral infection.Although the impact of SARS-CoV-2 in pregnancy remains to be determined,evidence indicates that the risk factors for severe COVID-19 are similar in pregnancy to the general population.Here we systemically analyzed the clinical characteristics of pregnant and non-pregnant female COVID-19 patients who were hospitalized during the same period and found that pregnant patients developed marked lymphopenia and higher inflammation evident by higher C-reactive protein and IL-6.To elucidate the pathways that might contribute to immunopathology or protective immunity against COVID-19 during pregnancy,we applied single-cell mRNA sequencing to profile peripheral blood mononuclear cells from four pregnant and six non-pregnant female patients after recovery along with four pregnant and three non-pregnant healthy donors.We found normal clonal expansion of T cells in the pregnant patients,heightened activation and chemotaxis in NK,NKT,and MAIT cells,and differential interferon responses in the monocyte compartment.Our data present a unique feature in both innate and adaptive immune responses in pregnant patients recovered from COVID-19.