Immune checkpoint ligands expressed on mature high endothelial venules predict poor prognosis of NSCLC: have a relationship with CD8+ T lymphocytes infiltration.

Background: An insufficient number of intratumoral CD8+ T lymphocytes is a major barrier to antitumor immunity and immunotherapy. High endothelial venules (HEVs) are the major sites through which lymphocytes enter tumors; however, the molecular mechanism through which HEVs mediate CD8+ T lymphocyte infiltration remains poorly understood. Methods: Forty-two patients with stage IIIA lung adenocarcinoma, who underwent surgery, were recruited. Multiplex immunohistochemical staining was conducted on tumor tissues to detect the immune checkpoint ligands (ICLs) expressed in the HEVs, blood vessels, and lymphatics. A new ICL score model was constructed to evaluate ligand expression. The relationship between ICL score, tumor-infiltrating CD8+ T cell frequency, and survival of patients was investigated. Results: Mature HEVs, but not blood vessels or lymphatics, mediated CD8+ T cell infiltration. However, the ICLs expressed on mature HEVs could negatively regulate CD8+ T cell entry into tertiary lymphoid structures (TLSs). In addition, according to the results obtained using our ICLtotal score model, the expression of ICLs on HEVs was observed to be a predictor of both CD8+ T cell infiltration and survival, in which a high ICLtotal score > 1 represent a weak CD8+ T cell infiltration and a high ICLtotal score > 2 predicts poor survival. Conclusion: Using the ICL score model, we discovered that ICLs expressed on HEVs are indicative of CD8+ T cell subset infiltration in TLSs, as well as of patient survival with lung cancer.

The spatial landscape of T cells in the microenvironment of stage III lung adenocarcinoma.

This study aimed to provide more information for prognostic stratification for patients through an analysis of the T-cell spatial landscape. It involved analyzing stained tissue sections of 80 patients with stage III lung adenocarcinoma (LUAD) using multiplex immunofluorescence and exploring the spatial landscape of T cells and their relationship with prognosis in the center of the tumor (CT) and invasive margin (IM). In this study, multivariate regression suggested that the relative clustering of CT CD4+ conventional T cell (Tconv) to inducible Treg (iTreg), natural regulatory T cell (nTreg) to Tconv, terminal CD8+ T cell (tCD8) to helper T cell (Th), and IM Treg to tCD8 and the relative dispersion of CT nTreg to iTreg, IM nTreg to nTreg were independent risk factors for DFS. Finally, we constructed a spatial immunological score named the GT score, which had stronger prognostic correlation than IMMUNOSCORE® based on CD3/CD8 cell densities. The spatial layout of T cells in the tumor microenvironment and the proposed GT score can reflect the prognosis of patients with stage III LUAD more effectively than T-cell density. The exploration of the T-cell spatial landscape may suggest potential cell-cell interactions and therapeutic targets and better guide clinical decision-making. © 2024 The Pathological Society of Great Britain and Ireland.

Dynamic carboxymethyl chitosan prodrug hydrogel precisely mediates robust therapy on wound infection.

Dynamic antibacterial polysaccharide prodrug hydrogels are in great demand for treatment of wound infection owing to their unique advantages such as excellent biocompatibility, superior antimicrobial property as well as favorable wound healing capacity. Herein, this work highlights the successful development of a dynamic carboxymethyl chitosan (CMC) prodrug hydrogel, which is facilely constructed through Schiffer base reaction between antibacterial components (amikacin and CMC) and crosslinker (dialdehyde PEG). Moderate dynamic imine linkages endow the hydrogel with excellent injectable and self-healing capability as well as targeted on-demand drug release in slightly alkaline condition at infected wound. All ingredients and their strong intermolecular interactions endow the hydrogel with favorable swelling and moisture retention capability. Moreover, the covalent and non-covalent interactions also endow the hydrogel with superior adhesion and mechanical property. These attractive characteristics enable hydrogel to effectively kill pathogens, promote wound healing and reduce side effects of amikacin. Thereby, such a dynamic CMC prodrug hydrogel may open a new avenue for a robust therapy on wound infection, greatly advancing their use in clinics.

Examining the spatial distribution of tumor-infiltrating immune cells in patients with stage I-IIIA LUAD.

This study aimed to examine the spatial distribution of immune cells by application of Gcross function in 170 patients with stage I-IIIA lung adenocarcinoma (LUAD) and explore its prognostic value. A total of 170 stage I-IIIA LUAD patients who underwent radical surgery were enrolled. Paraffinized tumor sections were collected for two panels of multicolor immunofluorescence staining as follows: Panel 1 (CD4, CD8, FOXP3, CD69, CD39, CD73, and DAPI) and Panel 2 (CD68, CD163, CD20, CD11c, PDL1, IDO, and DAPI). The immune cells were categorized as CD8+, CD4+ T-helper cell (CD4Th), Regulatory T cell (Treg), Macrophage type 1 (M1), Macrophage type 2 (M2), Dendritic cell (DC) and B cell. The immune cell numbers were enumerated, and the immune cell proximity score was calculated employing the Gcross function. The correlation between immune cell variables and Disease-Free Survival (DFS) was explored through univariate Cox regression analyses. Factors with P<0.05 were subjected to multivariate analyses. According to univariate Cox regression analyses, total PDL1+ and PDL1+ DC counts were negative factors (P=0.003, 0.031). CD4Th and IDO-DC counts were positive factors (P=0.022, 0.024). The proximity score (M1 to M2) was a positive factor for DFS (P=0.032), and the proximity score (PDL1+DC to M1) was a negative factor (P=0.009) according to univariate Cox analyses. In multivariate analyses, stage (IIIA vs. I+II) [HR: 1.77(1.18, 2.64), P=0.006] and proximity score (PDL1+DC to M1) [HR: 1.60(1.07, 2.37), P=0.021] were independent negative factors and CD4Th counts [HR: 0.60(0.40, 0.90), P=0.013] was an independent positive factor. Our study indicated that a higher level of tumor-infiltrating CD4Th cells predicted longer DFS, and a closer proximity of PDL1+ DCs to M1 cells was associated with dismal DFS in stage I-IIIA LUAD patients.

Synthesis of a novel photochemical and thermoresponsive diblock biomaterial with end-functionalized zinc porphyrin.

Porphyrin compound-based photochemical molecules and biomaterials have been synthesized for photosensitivity and bioimaging experiments. However, most porphyrin photosensitizers have limited application in biological environments owing to severe aggregation in aqueous solutions. In the present study, we prepared amphipathic and photosensitive copolymers using zinc porphyrin via consecutive atom transfer-free radical polymerizations (ATRPs) comprising photoresponsive and thermosensitive chain segments. Furthermore, we evaluated the photocatalytic activity of the copolymer for methylene blue (MB) in water. Methods: First, we synthesized a photoresponsive ain segment of poly (6-[4-(4-methoxyphenylazo)phenoxy]hexyl methacrylate) (ZnPor-PAzo); then, ZnPor-PAzo was used as a macroinitiator and was polymerized with N-isopropylacrylamide (NIPAM) via ATRPs to obtain a novel photochemical and thermoresponsive diblock biomaterial with end-functionalized zinc porphyrin [(ZnPor-PAzo)-PNIPAMs]. Results: The polydispersity index (M w/M n) of (ZnPor-PAzo)-PNIPAMs was 1.19-1.32. Furthermore, its photoresponsive and thermosensitive characteristics were comprehensively studied. Discussion: The end-functionalized diblock copolymer (ZnPor-PAzo)-PNIPAM exhibits obvious fluorescence and efficient photocatalytic activity for aqueous MB under visible light.

Blocking Tim-3 enhances the anti-tumor immunity of STING agonist ADU-S100 by unleashing CD4+ T cells through regulating type 2 conventional dendritic cells.

Rationale: An immunosuppressive tumor microenvironment (TME) is a major obstacle in tumor immunotherapy. Stimulator of interferon genes (STING) agonists trigger an inflammatory innate immune response to potentially overcome tumor immunosuppression. While STING agonists may hold promise as potential cancer therapy agents, tumor resistance to STING monotherapy has emerged in clinical trials, and the mechanisms remain unclear. Methods: The in vivo anti-tumor immunity of STING agonist ADU-S100 (S100), plus anti-T cell immunoglobulin and mucin-domain containing-3 antibody (αTim-3) were measured using murine tumor models. Tumor-specific T cell activation and alterations in the TME were detected using flow cytometry. The maturation and function of dendritic cells (DC) were also measured using flow cytometry, and the importance of CD4+ T cells in combination therapy was measured by blocking antibodies. Additionally, the effect of S100 on CD4+ T was verified via in vitro assays. Lastly, the impact of conventional dendritic cells (cDC) 2 with a high expression of Tim-3 on survival or therapeutic outcomes was further evaluated in human tumor samples. Results: S100 boosted CD8+ T by activating cDC1 but failed to initiate cDC2. Mechanistically, the administration of S100 results in an upregulation of Tim-3 expressed in cDC2 (Tim-3+cDC2) in both mice and humans, which is immunosuppressive. Tim-3+cDC2 restrained CD4+ T and attenuated the CD4+ T-driven anti-tumor response. Combining S100 with αTim-3 effectively promoted cDC2 maturation and antigen presentation, releasing CD4+ T cells, thus reducing tumor burden while prolonging survival. Furthermore, high percentages of Tim-3+cDC2 in the human TME predicted poor prognosis, whereas the abundance of Tim-3+cDC2 may act as a biomarker for CD4+ T quality and a contributing indicator for responsiveness to immunotherapy. Conclusion: This research demonstrated that blocking Tim-3 could enhance the anti-tumor immunity of STING agonist ADU-S100 by releasing CD4+ T cells through regulating cDC2. It also revealed an intrinsic barrier to ADU-S100 monotherapy, besides providing a combinatorial strategy for overcoming immunosuppression in tumors.

PD-1 blockade potentiates neoadjuvant chemotherapy in NSCLC via increasing CD127+ and KLRG1+ CD8 T cells.

The combination of PD-1 blockade with neoadjuvant chemotherapy (NAC) has achieved unprecedented clinical success in non-small cell lung cancer (NSCLC) compared to NAC alone, but the underlying mechanisms by which PD-1 blockade augments the effects of chemotherapy remain incompletely elucidated. Single-cell RNA sequencing was performed on CD45+ immune cells isolated from surgically resected fresh tumors of seven NSCLC patients receiving NAC or neoadjuvant pembrolizumab and chemotherapy (NAPC). Multiplex fluorescent immunohistochemistry was performed on FFPE tissues before and after NAC or NAPC from 65 resectable NSCLC patients, and results were validated with GEO dataset. NAC resulted in an increase only of CD20+ B cells, whereas NAPC increased the infiltration of CD20+ B cells, CD4+ T cells, CD4+CD127+ T cells, CD8+ T cells, CD8+CD127+ and CD8+KLRG1+ T cells. Synergistic increase in B and T cells promotes favorable therapeutic response after NAPC. Spatial distribution analysis discovered that CD8+ T cells and their CD127+ and KLRG1+ subsets were in closer proximity to CD4+ T/CD20+ B cells in NAPC versus NAC. GEO dataset validated that B-cell, CD4, memory, and effector CD8 signatures correlated with therapeutic responses and clinical outcomes. The addition of PD-1 blockade to NAC promoted anti-tumor immunity through T and B cells recruitment in the tumor microenvironment and induced tumor-infiltrating CD8+ T cells skewed toward CD127+ and KLRG1+ phenotypes, which may be assisted by CD4+ T cells and B cells. Our comprehensive study identified key immune cell subsets exerting anti-tumor responses during PD-1 blockade therapy and that may be therapeutically targeted to improve upon existing immunotherapies for NSCLC.

Galectin-9 expression clinically associated with mature dendritic cells infiltration and T cell immune response in colorectal cancer.

BACKGROUND: Galectin-9 is a member of the galectin family and has been reported to have a tumor-promoting or antitumor effect in response to the immune microenvironment. However, the immunomodulatory effect of galectin-9 in colorectal cancer (CRC) remains unclear. The antigen presentation and antitumor immune effects of galectin-9 in CRC were examined in this study. METHODS: The expression of galectin-9, dendritic cell markers (CD208 and CD1a), T-cell markers (CD3 and CD8) and mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) was assessed using immunohistochemistry in CRC samples. The correlation between galectin-9 and immune cells or immunomodulatory factors was also evaluated via multiple gene expression databases. RESULTS: The level of galectin-9 was decreased in mismatch repair-proficient patients compared with mismatch repair-deficient patients (p = 0.0335). GSEA showed that the regulatory mechanism of galectin-9 in CRC was related to a variety of immune pathways. Galectin-9 expression was strongly correlated with immune cell infiltration and immunomodulators (all p < 0.0001). In the relationship between galectin-9 expression and the infiltration of DCs, there was a negative correlation in CD1a + immature DCs (R = -0.263, p = 0.042). A strong positive correlation was observed in CD208 + mature DCs (R = 0.391, p < 0.01). Patients with high galectin-9 expression also exhibited abundant CD8 + T-cell and CD3 + T-cell infiltration. CONCLUSION: Collectively, our findings provide evidence that galectin-9 may increase the antitumor immune response of patients with CRC. DCs play an important role in galectin-9-mediated antitumor immune responses, which provides further insight into the development of immunotherapy.

Single-cell profiling of immune cells after neoadjuvant pembrolizumab and chemotherapy in IIIA non-small cell lung cancer (NSCLC).

The combination of immune checkpoint inhibitors (ICIs) with chemotherapy (chemoimmunotherapy) in the neoadjuvant setting have achieved favorable clinical benefits in non-small cell lung cancer (NSCLC), but the mechanism of clinical responses remain unclear. We provide a rich resource of 186,477 individual immune cells from 48 samples of four treatment-naive and eight neoadjuvant chemoimmunotherapy treated IIIA NSCLC patients (responders versus non-responders) by single-cell RNA-seq and TCR-seq. We observed the synergistic increase of B cells and CD4+ T cells were associated with a positive therapeutic response of neoadjuvant chemoimmunotherapy. B cell IgG subclasses IgG1 and IgG3 played a critical role in anti-tumor immune response in tumor lesions, and this process was driven by increased IL-21 secreted by infiltrated T follicular helper (Tfh) cells after neoadjuvant chemoimmunotherapy. Furthermore, we uncovered several critical events for positive clinical outcomes, including the diminished activated TNFRSF4+ regulatory T cells (Tregs), increased LAMP3+ dendritic cells (DCs), and the expansion of intratumoral CD4+ T clones and peripheral C3-Cytotoxic CD8+ T clones. A validation cohort of 26 treatment-naive and 30 neoadjuvant chemoimmunotherapy treated IIIA/ IIIB NSCLC patients verified these findings. In total, our comprehensive study of the single-cell profile of immune cells provides insights into mechanisms underlying anti-PD-1-based therapies and identified potential predictive factors and therapeutic targets for improving the efficiency of neoadjuvant chemoimmunotherapy in NSCLC.

Neoadjuvant chemoimmunotherapy in resectable stage IIIA/IIIB non-small cell lung cancer.

BACKGROUND: A small proportion of patients with non-small cell lung cancer (NSCLC) experience objective clinical benefit after neoadjuvant programmed cell death 1 (PD-1) blockade. A neoadjuvant therapeutic regimen combining immune checkpoint blockade with chemotherapy might improve the treatment effect, but such a regimen has not been tested in patients with resectable stage IIIA/IIIB NSCLC. METHODS: A retrospective study of 35 patients with resectable stage IIIA and IIIB NSCLC who were treated with neoadjuvant chemoimmunotherapy (NCIO) was performed. Patients were evaluated for pathological complete response (pCR), major pathologic response (MPR), safety, and feasibility. The correlations of pathologic response with various clinical factors were studied to identify predictors of pathological response. RESULTS: NCIO was associated with few immediate adverse events. NCIO did not delay planned surgery and led to a pCR rate of 51.43% and an MPR rate of 74.29% for the primary tumor. No association was observed between programmed death-ligand 1 (PD-L1) expression before NCIO and the pathologic response (Pearson's r=-0.071; P=0.685). However, a significant difference was observed in pathological response in patients with intracavitary and extracavitary tumors (P<0.05). Patients with intracavitary type had a higher pCR (76.47% vs. 31.58%) and MPR (100% vs. 50.00%) rate than patients with extracavitary type (Pearson's r=0.7280; P=0.0009). CONCLUSIONS: NCIO was associated with few side effects, did not delay surgery, and achieved a pCR in 51.43% and MPR in 74.29% of resected tumors. No significant correlation was found between pathologic response and PD-L1 expression. While the intracavitary and extracavitary tumors type T was predictive of the pathological response to NCIO.

Single-Cell Sequencing Reveals the Transcriptome and TCR Characteristics of pTregs and in vitro Expanded iTregs.

Regulatory T cells (Tregs) play a critical role in the maintenance of immune tolerance and tumor evasion. However, the relative low proportion of these cells in peripheral blood and tissues has hindered many studies. We sought to establish a rapamycin-based in vitro Treg expansion procedure in patients diagnosed with colorectal cancer and perform single-cell sequencing to explore the characteristics of Treg cells. CD25+ cells enriched from peripheral blood mononuclear cells (PBMC) of colorectal tumor patients were cultured in X-VIVO15 medium, supplemented with 5% human AB serum, L-glutamine, rapamycin, interleukin-2 (IL-2), and Dynabeads human Treg expander for 21 days to expand Tregs. Treg cells with satisfactory phenotype and function were successfully expanded from CD4+CD25+ cells in patients with colorectal cancer. The median expansion fold was 75 (range, 20-105-fold), and >90.0% of the harvest cells were CD4+CD25+CD127dim/- cells. The ratio of CD4+CD25+Foxp3+ cells exceeded 60%. Functional assays showed that iTregs significantly inhibited CD8+T cell proliferation in vitro. Single-cell sequencing showed that the transcriptome of pTreg (CD4+CD25+CD127dim/- cells isolated from PBMC of colorectal cancer patients) and iTreg (CD4+CD25+CD127dim/- cells expanded in vitro according to the above regimen) cells were interlaced. pTregs exhibited enhanced suppressive function, whereas iTregs exhibited increased proliferative capacity. TCR repertoire analysis indicated minimal overlap between pTregs and iTregs. Pseudo-time trajectory analysis of Tregs revealed that pTregs were a continuum composed of three main branches: activated/effector, resting and proliferative Tregs. In contrast, in vitro expanded iTregs were a mixture of proliferating and activated/effector cells. The expression of trafficking receptors was also different in pTregs and iTregs. Various chemokine receptors were upregulated in pTregs. Activated effector pTregs overexpressed the chemokine receptor CCR10, which was not expressed in iTregs. The chemokine CCL28 was overexpressed in colorectal cancer and associated with poor prognosis. CCR10 interacted with CCL28 to mediate the recruitment of Treg into tumors and accelerated tumor progression. Depletion of CCR10+Treg cells from tumor microenvironment (TME) could be used as an effective treatment strategy for colorectal cancer patients. Our data distinguished the transcriptomic characteristics of different subsets of Treg cells and revealed the context-dependent functions of different populations of Treg cells, which was crucial to the development of alternative therapeutic strategies for Treg cells in autoimmune disease and cancer.

Autologous cytokine-induced killer (CIK) cells enhance the clinical response to PD-1 blocking antibodies in patients with advanced non-small cell lung cancer: A preliminary study.

BACKGROUND: Programmed death-1 (PD-1) blocking antibodies have been shown to improve progression-free survival (PFS) and overall survival in a subset of patients with non-small cell lung cancer (NSCLC). However, the objective response rate with these agents remains low, and the vast majority of NSCLC patients require alternative combination treatment regimens to prolong their survival. The purpose of this study was to evaluate the clinical efficacy of autologous cytokine-induced killer (CIK) cell infusions combined with PD-1 blocking antibodies in patients with NSCLC. METHODS: In this preliminary study, we investigated the safety and immune function effectiveness of PD-1 blockade antibodies pembrolizumab or nivolumab administered in combination with or without autologous CIK cell infusions in 18 patients with advanced NSCLC. The peripheral blood mononuclear cells were isolated from these patients and the expression level of some cell surface molecules like PD-1 were detected using flow cytometry to reflect the effectiveness of this combination regimen. RESULTS: No treatment-related deaths occurred in either cohort. In comparison with the pretreatment level, CD3+ CD56+ CD16+ T cells were significantly increased with the combination therapy, while myeloid-derived suppressor cells were significantly increased with PD-1 blocking antibody therapy alone but not with combination therapy. Although the serum interleukin-4 level was downregulated following treatment with the combination regimen, interferon-γ levels were unchanged. CONCLUSIONS: The purpose of this clinical study was to report the clinical efficacy and lack of exacerbated autoimmune adverse events with a combination of PD-1 blockade and CIK cell infusions in patients with advanced NSCLC, further supporting assessments of this combination in future clinical trials.

Feasibility of sleeve lobectomy after neo-adjuvant chemo-immunotherapy in non-small cell lung cancer.

Immunotherapy is one of the most effective treatments for patients with advanced lung cancer. In many advanced non-small cell lung cancer (NSCLC) cases, the tumor is centrally located. For such patients, sleeve lobectomy has been considered as a more effective therapeutic option compared with pneumonectomy, achieving better long-term survival and quality of life with no increase in morbidity or mortality. Until now, there have been no studies regarding the efficacy and safety of neo-adjuvant chemo-immunotherapy prior to sleeve lobectomy for lung cancer. From January 2019 through October 2019, nine patients were diagnosed as NSCLC and evaluated to undergo sleeve lobectomy surgery (SLS). Of these patients, four received two cycles of pembrolizumab plus paclitaxel and cisplatin (PPC) followed by sleeve lobectomy, while five patients underwent SLS alone. The patients' clinical characteristics, perioperative parameters, and postoperative outcomes were analyzed. Multiplex fluorescent immunohistochemistry was performed to determine the number of macrophages, CD4+ and CD8 T cells, and Treg cells in the bronchial mucosa. Three of the four patients achieved a complete pathological response [0% viable tumor, pathologic complete response (pCR)]. All of the patients in the PPC group achieved major pathological response (≤10% viable tumor, MPR). No grade 3 or 4 treatment-related adverse events occurred in the PPC group, nor did any of the patients in the group experience treatment-related surgical delays. The mean surgical time and the number of lymph nodes dissected were the same in the two groups. The PPC group had a higher number of CD8 + T cells compared to the SLS group (P<0.01). No postoperative chylothorax, pneumonia, or other postoperative complications occurred in either group. The surgical difficulty and post-surgical complication rate of sleeve lobectomy with neo-adjuvant chemo-immunotherapy were similar to those of SLS alone. Neo-adjuvant chemo-immunotherapy is effective and safe with sleeve lobectomy for NSCLC patients. Additional prospective multi-center randomized studies using larger patient cohorts are necessary to validate our findings.

Primary tumor standardized uptake value (SUVmax) measured on 18F-FDG PET/CT and mixed NSCLC components predict survival in surgical-resected combined small-cell lung cancer.

PURPOSE: The combined small-cell lung cancer (c-SCLC) is rare and has unique clinicopathological futures. The aim of this study is to investigate 18F-FDG PET/CT parameters and clinicopathological factors that influence the prognosis of c-SCLC. METHODS: Between November 2005 and October 2014, surgical-resected tumor samples from c-SCLC patients who received preoperative 18F-FDG PET/CT examination were retrospectively reviewed. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were used to evaluate metabolic parameters in primary tumors. The survivals were evaluated with the Kaplan-Meier method. Univariate and multivariate analyses were used to evaluate potential prognostic factors. RESULTS: Thirty-one patients were enrolled, with a median age of 62 (range: 35 - 79) years. The most common mixed component was squamous cell carcinoma (SCC, n = 12), followed by large-cell carcinoma (LCC, n = 7), adenocarcinoma (AC, n = 6), spindle cell carcinoma (n = 4), adenosquamous carcinoma (n = 1) and atypical carcinoid (n = 1). The median follow-up period was 53.0 (11.0-142.0) months; the 5-year overall survival (OS) and progression-free survival(PFS) rate were 48.4% and 35.5%, respectively. Univariate survival analysis showed that gender, smoking history, tumor location were associated with PFS (P = 0.036, P = 0.043, P = 0.048), SUVmax and TNM stage were closely related to PFS in both Mixed SCC and non-SCC component groups (P = 0.007, P = 0.048). SUVmax, smoking history, tumor size and mixed SCC component were influencing factors of OS in patients (P = 0.040, P = 0.041, P = 0.046, P = 0.029). Multivariate survival analysis confirmed that TNM stage (HR = 2.885, 95%CI: 1.323-6.289, P = 0.008) was the most significantly influential factor for PFS. High SUVmax value (HR = 9.338, 95%CI: 2.426-35.938, P = 0.001) and mixed SCC component (HR = 0.155, 95%CI: 0.045-0.530, P = 0.003) were poor predictors for OS. CONCLUSION: Surgical-resected c-SCLCs have a relatively good prognosis. TNM stage is the most significant factor influencing disease progression in surgical-resected c-SCLCs. SUVmax and mixed NSCLC components within c-SCLCs had a considerable influence on the survival. Both high SUVmax and mixed SCC component are poor predictors for patients with c-SCLCs.

Solution Processable CrN Thin Films: Thickness-Dependent Electrical Transport Properties.

Thickness is a very important parameter with which to control the microstructures, along with physical properties in transition-metal nitride thin films. In work presented here, CrN films with different thicknesses (from 26 to 130 nm) were grown by chemical solution deposition. The films are pure phase and polycrystalline. Thickness dependence of microstructures and electrical transport behavior were studied. With the increase of films thickness, grain size and nitrogen content are increased, while resistivity, zero-field sensitivity and magnetoresistance are decreased. In the temperature range of 5-350 K, all samples exhibited semiconductor-like properties with dρ/dT < 0. For the range above and below the Néel temperature, the resistivity can be fitted by the thermal activation model and the two-dimensional weak localization (2D-WL) model, respectively. The ultra-low magnetoresistance at a low temperature under high magnetic fields with a large zero-field sensitivity was observed in the CrN thin films. The zero-field sensitivity can be effectively tuned to 10-2 K-1 at 5 K with a magnetoresistance of less than 1% at 2 K under 14 T by reasonably controlling the thickness.

Self-Assembly of CdS/CdIn2S4 Heterostructure with Enhanced Photocascade Synthesis of Schiff Base Compounds in an Aromatic Alcohols and Nitrobenzene System with Visible Light.

A series of novel CdS/CdIn2S4 composite materials were prepared via a one-pot solvothermal process. The as-obtained photocatalysts were characterized by several techniques and the photocatalytic properties of CdS/CdIn2S4 photocatalysts were studied by photocascade synthesis of Schiff base compounds in a photocatalytic reaction system of aromatic alcohols and nitrobenzene irradiated with visible light. The results reveal that the resulting CdS/CdIn2S4 heterostructure samples show outstanding photocatalytic activities toward the photocascade production of Schiff base compounds in an aromatic alcohols and nitrobenzene reaction system irradiated with visible light. An optimized 50.0% CdS/CdIn2S4 heterostructure sample shows the highest Schiff base yield of 42.0% irradiated with visible light for 4 h, which is approximately 19.1 and 1.54 times higher than those of sole CdS and CdIn2S4 samples, respectively. The fabrication of heterogeneous structure improves the spatial separation and migration of photoinduced electron-hole pairs, thus contributing to the enhancement of photocatalytic properties. We foresee that this finding can offer a strategy to develop heterostructure composites for efficient synthesis of organics by photocatalysis under mild conditions.

Efficient utilization of photogenerated electrons and holes for photocatalytic redox reactions using visible light-driven Au/ZnIn2S4 hybrid.

In this study, a new photocatalytic reaction system for simultaneous selective oxidation of aromatic alcohols to corresponding aldehydes and reduction of protons to H2 has been developed. The results reveal that compared with pure ZnIn2S4, the ZnIn2S4 photocatalysts modified with noble metal gold (Au/ZnIn2S4) significantly promote the photocatalytic performance. Among them, the 0.5% Au/ZnIn2S4 nanosheets shows the highest photocatalytic activity for selective oxidation of benzyl alcohol to benzaldehyde and hydrogen production, and the yields of H2 and benzaldehyde are 326.68 and 352.04 µmol under visible light irradiation for 4 h, respectively. Those are about 4.4 and 3.6 times higher than those of pure ZnIn2S4 sample (74.0 µmol H2 and 98.04 µmol benzaldehyde), respectively. The utilization ratio of photogenerated electrons to holes can achieve 92.8%. Additionally, the control experiments demonstrate that the photogenerated electrons and holes play significant roles during the reaction process. It is hoped that the current work can offer an avenue to utilize the photogenerated carriers more efficiently and to develop other photocatalytic reaction systems, such as nitrogen fixation and reduction of carbon dioxide.

Cytokine-induced killer cell therapy for the treatment of primary hepatocellular carcinoma subsequent to liver transplantation: A case report.

Liver cancer, of which the most common form is hepatocellular carcinoma (HCC), is one of the most lethal cancers worldwide. Immunotherapy based on the direct attack of tumor cells and the stimulation of an antitumor immune response may represent a novel strategy to control HCC recurrence and metastasis. The present study reports the case of a patient with HCC, and describes the safety and feasibility of successful administration with a mass of autologous activated T cells on numerous occasions subsequent to liver transplantation (LT), in order to kill the residual tumor cells and stimulate the immune system. A large number of infused activated T cells may pose a potential risk to the allograft. However, no acute or delayed adverse effects of cytokine-induced killer cell (CIK) therapy, or other symptoms of secondary acute host-versus-graft disease (HVGD), were observed. These observations demonstrate the relatively low toxicity of CIK infusion to a patient that has undergone LT, and more importantly, they demonstrate the feasibility of this immunotherapy for the patient, following successful LT.

Rapid Response of Advanced Squamous Non-Small Cell Lung Cancer with Thrombocytopenia after First-Line Treatment with Pembrolizumab Plus Autologous Cytokine-Induced Killer Cells.

We present the first clinical evidence of advanced squamous non-small cell lung cancer with severe thrombocytopenia showing dramatic improvement after first-line treatment with pembrolizumab plus autologous cytokine-induced killer cells.

Epitaxial antiperovskite superconducting CuNNi3 thin films synthesized by chemical solution deposition.

Epitaxial antiperovskite superconducting CuNNi3 thin films have been grown by chemical solution deposition. The film is a type II superconductor and shows a Tc of 3.2 K with a transition of 0.13 K. The Hc2(0) and ξ0 are estimated to be 8.1 kOe and 201 Å, respectively.