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.

Heterogeneous integration of contact-printed semiconductor nanowires for high-performance devices on large areas

In this work,we have developed a contact-printing system to efficiently transfer the bottom-up and top-down semiconductor nanowires(NWs),preserving their as-grown features with a good control over their electronic properties.In the close-loop configuration,the printing system is controlled with parameters such as contact pressure and sliding speed/stroke.Combined with the dry pre-treatment of the receiver substrate,the system prints electronic layers with high NW density(7 NWs/μm for bottom-up ZnO and 3 NWs/μm for top-down Si NWs),NW transfer yield and reproducibility.We observed compactly packed(~115 nm average diameters of NWs,with NW-to-NW spacing~165 nm)and well-aligned NWs(90%with respect to the printing direction).We have theoretically and experimentally analysed the role of contact force on NW print dynamics to investigate the heterogeneous integration of ZnO and Si NWs over pre-selected areas.Moreover,the contact-printing system was used to fabricate ZnO and Si NW-based ultraviolet(UV)photodetectors(PDs)with Wheatstone bridge(WB)configuration on rigid and flexible substrates.The UV PDs based on the printed ensemble of NWs demonstrate high efficiency,a high photocurrent to dark current ratio(>10^(4))and reduced thermal variations as a result of inherent self-compensation of WB arrangement.Due to statistically lesser dimensional variations in the ensemble of NWs,the UV PDs made from them have exhibited uniform response.

Angle-selective perfect absorption with two-dimensional materials

Two-dimensional(2D)materials have great potential in photonic and optoelectronic devices.However,the relatively weak light absorption in 2D materials hinders their application in practical devices.Here,we propose a general approach to achieve angleselective perfect light absorption in 2D materials.As a demonstration of the concept,we experimentally show giant light absorption by placing large-area single-layer graphene on a structure consisting of a chalcogenide layer atop a mirror and achieving a total absorption of 77.6%in the mid-infrared wavelength range(~13μm),where the graphene contributes a record-high 47.2%absorptivity of mid-infrared light.Construction of such an angle-selective thin optical element is important for solar and thermal energy harvesting,photo-detection and sensing applications.Our study points to a new opportunity to combine 2D materials with photonic structures to enable novel device applications.

Development of a highly controlled system for large-area,directional printing of quasi-1D nanomaterials

Printing is a promising method for the large-scale,high-throughput,and low-cost fabrication of electronics.Specifically,the contact printing approach shows great potential for realizing high-performance electronics with aligned quasi-1D materials.Despite being known for more than a decade,reports on a precisely controlled system to carry out contact printing are rare and printed nanowires(NWs)suffer from issues such as location-to-location and batch-to-batch variations.To address this problem,we present here a novel design for a tailor-made contact printing system with highly accurate control of printing parameters(applied force:0-6 N±0.3%,sliding velocity:0-200 mm/s,sliding distance:0-100 mm)to enable the uniform printing of nanowires(NWs)aligned along 93%of the large printed area(1 cm^(2)).The system employs self-leveling platforms to achieve optimal alignment between substrates,whereas the fully automated process minimizes human-induced variation.The printing dynamics of the developed system are explored on both rigid and flexible substrates.The uniformity in printing is carefully examined by a series of scanning electron microscopy(SEM)images and by fabricating a 5×5 array of NW-based photodetectors.This work will pave the way for the future realization of highly uniform,large-area electronics based on printed NWs.

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.