Adding PD-1 blockade in the neoadjuvant regimens for locally advanced rectal cancer (LARC) patients with microsatellite stable (MSS) / mismatch repair-proficient (pMMR) tumors is an attractive, but debatable strategy. This phase 2, multicenter, prospective, single-arm study enrolled patients from 6 centers from June 2021 to November 2022. Locally advanced rectal cancer (LARC, cT_3-4aN₀M₀ and cT_1-4aN_1-2M₀) patients aged ≥18 years with the distance from distal border of tumor to anal verge ≤10 cm (identified by Magnetic Resonance Imaging) were qualified for inclusion. The patients received long-course radiotherapy (50 Gy/25 fractions, 2 Gy/fraction, 5 days/week) and three 21-day cycles capecitabine (850–1000 mg/m2, bid, po, day1–14) and three 21-day cycles tislelizumab (200 mg, iv.gtt, day8) as neoadjuvant. Total mesorectal excision (TME) was 6–12 weeks after the end of radiotherapy to achieve radical resection. A total of 50 patients were enrolled in this study. The pathological complete response rate was 40.0% [20/50, 95% confidence interval (CI): 27.61–53.82%], while 15 (30.0%, 95% CI: 19.1–43.75%), 9 (18.0%, 95% CI: 9.77–30.8%), 2 (4.0%, 95% CI: 1.10–13.46%) patients respectively achieved grade 1, 2, and 3 tumor regression. Treatment-related adverse events (TRAEs) occurred in 28 (56.0%) LARC patients, including 26(52.0%) with grade I-II and 2 (4.0%) with grade III (1 with grade 3 immune-related colitis and 1 with grade 3 rash). PD-1 blockade plus long-course chemoradiotherapy (CRT) showed promising therapeutic effects according to pathological complete response rate and is well-tolerated in LARC patients. A larger randomized controlled study is desired to further validate the above findings.

Cancer immunotherapy has revolutionized oncology by leveraging the immune system to combat tumors. Among various biomarkers, neoantigens and tumor mutational burden (TMB) have emerged as critical factors in tailoring personalized treatments. Neoantigens are tumor-specific peptides displayed on cancer cell surfaces, derived from somatic mutations. Recognized as "non-self" by the immune system, they trigger T-cell responses and enable therapies like personalized vaccines and adoptive T-cell transfer. Critically, neoantigen potential correlates with TMB, which quantifies the total somatic mutations within a tumor genome. A higher TMB generally correlates with a greater likelihood of generating immunogenic neoantigens, making it a predictive biomarker for the efficacy of immune checkpoint inhibitors (ICI). Progress in high-throughput sequencing, bioinformatics, and immuno-peptidomics has significantly enhanced the accuracy of neoantigen prediction, including assessments of major histocompatibility complex (MHC) binding affinity and T-cell receptor recognition. Clinically, neoantigen-based therapies have shown efficacy in early trials, with strategies such as mRNA vaccines demonstrating synergy with ICI by boosting T-cell activation and overcoming immune suppression. Combining neoantigen-based therapies with chemotherapy and radiotherapy harnesses synergistic mechanisms to enhance efficacy, overcome resistance, and emerge as a pivotal oncology research focus. The integration of TMB into clinical practice has received regulatory approval as a biomarker for stratifying patients for ICI therapies. Furthermore, advanced methodologies like liquid biopsy and single-cell technologies have streamlined TMB measurement, improving its predictive value for personalized immunotherapy. Collectively, neoantigens and TMB have optimized the evolution of precision immuno-oncology by providing frameworks that maximize therapeutic efficacy, overcome resistance mechanisms, and advance durable cancer remission.​

Wound dressing is an important tool for wound management. Designing wound dressings by combining various novel materials and drugs to optimize the peri-wound environment and promote wound healing is a novel concept. Hydrogels feature good ductility, high water content, and favorable oxygen transport, which makes them become some of the most promising materials for wound dressings. In addition, nanomaterials exhibit superior biodegradability, biocompatibility, and colloidal stability in wound healing and can play a role in promoting healing through their nanoscale properties or as carriers of other drugs. By combining the advantages of both technologies, several outstanding and efficient wound dressings have been developed. In this paper, we classify nano-based hydrogel dressings into four categories: hydrogel dressings loaded with a nanoantibacterial drug; hydrogel dressings loaded with oxygen-delivering nanomedicines; hydrogel dressings loaded with nanonucleic acid drugs; and hydrogel dressings loaded with other nanodelivered drugs. The design ideas, advantages, and challenges of these nano-based hydrogel wound dressings are reviewed and analyzed. Finally, we envisaged possible future directions for wound dressings in the context of relevant scientific and technological advances, which we hope will inform further research in wound management.

Mesenchymal stem cells (MSCs) have been recognized as a cell therapy with the potential to promote skin healing. MSCs, with their multipotent differentiation ability, can generate various cells related to wound healing, such as dermal fibroblasts (DFs), endothelial cells, and keratinocytes. In addition, MSCs promote neovascularization, cellular regeneration, and tissue healing through mechanisms including paracrine and autocrine signaling. Due to these characteristics, MSCs have been extensively studied in the context of burn healing and chronic wound repair. Furthermore, during the investigation of MSCs, their unique roles in skin aging and scarless healing have also been discovered. In this review, we summarize the mechanisms by which MSCs promote wound healing and discuss the recent findings from preclinical and clinical studies. We also explore strategies to enhance the therapeutic effects of MSCs. Moreover, we discuss the emerging trend of combining MSCs with tissue engineering techniques, leveraging the advantages of MSCs and tissue engineering materials, such as biodegradable scaffolds and hydrogels, to enhance the skin repair capacity of MSCs. Additionally, we highlight the potential of using paracrine and autocrine characteristics of MSCs to explore cell-free therapies as a future direction in stem cell-based treatments, further demonstrating the clinical and regenerative aesthetic applications of MSCs in skin repair and regeneration.

CD4 and CD8 coreceptor double negative TCRαβ+ T (DNT) cells are increasingly being recognized for their critical and diverse roles in the immune system. However, their molecular and functional signatures remain poorly understood and controversial. Moreover, the majority of studies are descriptive because of the relative low frequency of cells and non-standardized definition of this lineage. In this study, we performed single-cell RNA sequencing on 28,835 single immune cells isolated from mixed splenocytes of male C57BL/6 mice using strict fluorescence-activated cell sorting. The data was replicated in a subsequent study. Our analysis revealed five transcriptionally distinct naïve DNT cell clusters, which expressed unique sets of genes and primarily performed T helper, cytotoxic and innate immune functions. Anti-CD3/CD28 activation enhanced their T helper and cytotoxic functions. Moreover, in comparison with CD4+, CD8+ T cells and NK cells, Ikzf2 was highly expressed by both naïve and activated cytotoxic DNT cells. In conclusion, we provide a map of the heterogeneity in naïve and active DNT cells, addresses the controversy about DNT cells, and provides potential transcription signatures of DNT cells. The landscape approach herein will eventually become more feasible through newer high throughput methods and will enable clustering data to be fed into a systems analysis approach. Thus the approach should become the "backdrop" of similar studies in the myriad murine models of autoimmunity, potentially highlighting the importance of DNT cells and other minor lineage of cells in immune homeostasis. The clear characterization of functional DNT subsets into helper DNT, cytotoxic DNT and innate DNT will help to better understand the intrinsic roles of different functional DNT subsets in the development and progression of autoimmune diseases and transplant rejection, and thereby may facilitate diagnosis and therapy.