Objective To evaluate the efficacy and safety of a combination therapy regimen comprising stereotactic body radiation therapy (SBRT) combined with liposomal irinotecan, camrelizumab, and anti-angiogenic therapy (CAP) in patients with advanced bone and soft tissue sarcomas. Methods This study is a prospective subgroup analysis of the multicenter, open-label, single-arm phase Ⅱ CAP trial (NCT04569916), which enrolled 60 patients with advanced solid tumors who had progressed after standard therapy between November 2020 and February 2023, including 11 patients with advanced bone and soft tissue sarcomas. All patients received sequential liposomal irinotecan within 48 hours after stereotactic body radiotherapy (SBRT), followed by maintenance therapy with camrelizumab and an anti-angiogenic agent until disease progression or intolerable toxicity. The primary efficacy endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results In the bone and soft tissue sarcoma subgroup (n=11), three patients achieved partial response (PR), five had stable disease (SD), and three experienced disease progression (PD). ORR was 27.3%, and DCR was 72.7%. mPFS was 5.8 months (95%CI: 2.2-10.3), and mOS not reached. Regarding safety, adverse reactions primarily included bone marrow suppression, fatigue, and gastrointestinal reactions, indicating overall manageable toxicity. Conclusion As a subgroup analysis of the CAP study, this research suggests that radiotherapy combined with liposomal irinotecan, camrelizumab, and anti-angiogenic therapy demonstrates certain efficacy in advanced bone and soft tissue sarcomas that have failed multiple lines of treatment, with overall manageable adverse reactions. Future studies should expand the sample size.

Probiotics are natural systems bridging synthetic biology, physical biotechnology, and immunology, initiating innate and adaptive anti-tumor immune activity. We previously constructed an all-in-one engineered food-grade probiotic Lactococcus lactis (FOLactis) which could boost the crosstalk among different immune cells such as dendritic cells (DCs), natural killer cells, and T cells. Herein, considering the limited clinical efficacy of naked personalized neoantigen peptide vaccines, we decorate FOLactis with tumor antigens by employing a Plug-and-Display system comprising membrane-inserted peptides. Intranodal injection of FOLactis coated with neoantigen peptides (Ag-FOLactis) induces robust DCs presentation and neoantigen-specific cellular immunity. Notably, Ag-FOLactis not only triggers a 45-fold rise in the quantity of locally reactive neoantigen-specific T cells but also induces epitope spreading in both subcutaneous and metastatic tumor-bearing models, leading to potent inhibition of tumor growth. These findings imply that Ag-FOLactis represents a powerful platform to rapidly and easily display antigens, facilitating the development of a bio-activated platform for personalized therapy.

Colorectal cancer （CRC） ranks as the second leading cause of cancer death worldwide. Although preventive colonoscopy screening has improved the survival rate of CRC patients in the past few years， there are still many patients diagnosed after symptoms appear. The surgery for CRC carries high risks and high recurrence， and ideal therapies remain to be developed. The Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway has become a focus of research due to its central role in cellular activities. As a classic oncogenic pathway， the JAK/STAT signaling pathway offers new possibilities for diagnosing and treating various malignancies， and it paves a new way for developing therapies for CRC. This pathway not only participates in basic cellular processes， such as proliferation， differentiation， and apoptosis but also plays a crucial role in immune responses and inflammation. Abnormal activation of the JAK/STAT signaling pathway is closely related to the occurrence and development of CRC. Studies have shown that the active components and compound prescriptions of traditional Chinese medicine （TCM） can inhibit the proliferation， invasion， migration， and angiogenesis while promoting the apoptosis and autophagy of CRC cells by interfering with the JAK/STAT signaling pathway. Furthermore， this pathway may also play a role in regulating the sensitivity of tumor cells to chemotherapy and radiotherapy， thus influencing the effectiveness of tumor treatment and impeding the progression of CRC. In recent years， research results have been updated rapidly， and previous literature summaries have failed to incorporate the latest findings， creating obstacles to accessing current literature. Therefore， this article supplements and summarizes information from the definition of the JAK/STAT pathway， association of this pathway with CRC， and TCM intervention of CRC. This review aims to provide references for future development of molecular biology regarding CRC and the research and development of new drugs.

Tumor immunotherapy has achieved breakthroughs in the treatment of malignant tumors by activating the host immune system’s antitumor response mechanism. Among various strategies, Toll-like receptor (TLR) agonists have garnered substantial attention due to their unique immunomodulatory capabilities. This work reviews the research progress on the combination of TLR agonists with radiotherapy in tumor immunotherapy, focusing on the clinical translational potential of intratumoral injection strategies. Clinical studies have shown that the in-situ injection of TLR agonists in combination with radiotherapy can effectively suppress primary and metastatic lesions by inducing immunogenic cell death, releasing tumor antigens, activating local immune responses, and triggering abscopal effects. Moreover, novel extended-release formulations and “endogenous vaccine” designs further enhance the safety and durability of treatment. Despite several challenges such as tumor microenvironment suppression and dose optimization, TLR agonists hold promise for the treatment of “cold” tumors lacking innate immunity through combinations with immune checkpoint inhibitors, nanodelivery technologies, and precise biomarker screening.

In situ tumor vaccine has become an important strategy in cancer immunotherapy owing to its ability to induce immune responses locally and overcome tumor heterogeneity. However, the abnormal structure and mechanical properties of the tumor’s physical microenvironment significantly limit the efficiency of vaccine delivery and immune efficacy. In this review, the key factors in the tumor’s physical microenvironment, including solid pressure, interstitial fluid pressure, matrix stiffness, and tissue microstructure, are systematically discussed. Their obstructive roles in immune cell infiltration, antigen presentation, and immune activation are analyzed. The potential of approaches, such as radiotherapy, anti-angiogenic therapy, extracellular matrix degradation agents, nanomaterials, and hydrogel delivery platforms, in reshaping the tumor’s physical microenvironment is explored. This review aims to offer theoretical and practical guidance for optimizing in situ vaccine strategies through the regulation of the tumor’s physical microenvironment, ultimately advancing the precision and effectiveness of cancer immunotherapy.

Objective:To explore the prognosis of patients with gastric cancer peritoneal metastasis (PM) receiving programmed cell death-1 (PD-1) antibody therapy, and investigate the biomarkers that affect the prognosis of anti-PD-1 therapy.Methods:This restrospecific study collected the clinic-pathological data of 56 patients with peritoneal metastasis of gastric cancer who received first-line treatment in the Nanjing Drum Town Hospital from March 2020 to September 2023, among which 41 had received anti-PD-1 immunotherapy and 15 hadn't. The relationship between overall survival (OS) and anti-PD-1 immunotherapy was evaluated by Kaplan-Meier analysis. The relationship between baseline peripheral blood indicators and treatment response of patients with anti-PD-1 treatment was analyzed using unpaired t-test. Subsequently, the Cox proportional risk regression model was used to explore the clinical prognostic factors that may affect anti-PD-1 immunotherapy by univariate and multivariate analysis. The clinical prognostic factors included baseline data and baseline peripheral blood indexes such as anti-PD-1 treatment lines, Eastern Cooperative Oncology Group performance status (ECOG PS), combined positive score (CPS), expression of human epidermal growth factor receptor 2 (Her-2), EBER status, pathological types, other metastatic lesions, ascites content before immunotherapy, with or without abdominal drainage during anti-PD-1 treatment, blood lipid indicators, inflammatory indicators, and tumor indicators. Results:Kaplan-Meier survival statistics showed similar OS (15.9 vs. 15.2 months, P=0.600) in patients with anti-PD-1 therapy compared to those without anti-PD-1 therapy. Patients with baseline high-density lipoprotein (HDL) ≥0.97 mmol/L ( n=22) demonstrated a significantly longer median OS compared to those with HDL＜0.97 mmol/L (15.2 vs. 13.5 months; P=0.018). Similarly, the cohort with apolipoprotein A1 (ApoA1) levels ≥0.86 g/L ( n=21) showed superior survival outcomes, with a median OS of 17.7 months versus 12.3 months in the ApoA1＜0.86 g/L group ( n=20; P=0.006). In contrast, elevated baseline alpha-fetoprotein (AFP) levels ( n=2) were associated with markedly reduced survival (median OS: 5.7 vs. 15.2 months in normal AFP group, n=37; P=0.005). Notably, elevated pretreatment ApoA1 levels correlated with enhanced immunotherapy response ( P=0.017). Multivariate Cox regression analysis revealed that ApoA1 deficiency (≥0.86 g/L) independently predicted better OS following PD-1 antibody therapy ( HR=0.35, 95% CI: 0.12-0.98, P=0.046) in gastric cancer patients with PM. Conclusions:In our study, it is first proposed that ApoA1 could be a significant predictor of the survival advantages of immunotherapy in gastric cancer patients with PM.

Tumour neoantigen sprimarily refer to a specific group of tumour antigens derived from tumour mutant proteins, but also including antigens generated by the oncogenic viruses integrated into the genome, which are not expressed by normal cells in the human body but are specifically expressed in tumor cells, and are capable of triggering the tumour-specific cellular and humoral immunity in the host. In recent years, significant advances in tumor immunotherapy such as therapeutic oncology vaccines, and adoptive cell therapy (ACT) have been acquired. However, standalone tumor therapeutic vaccines exhibit several drawbacks. They possess low immunogenicity, face a substantial tumor burden, and are highly susceptible to the immunosuppressive microenvironment. Consequently, when applied in isolation during clinical practice, their therapeutic efficacy remains limited. Compared with immunotherapies such as immune checkpoint inhibitors and tumor vaccines, ACT is less affected by the immunosuppressive microenvironment in the body and can generate a sufficient number of killer cells. The crux of ACT lies in the generation of immunogenic tumor-specific killer cells. Neoantigens enhance the immunogenicity and anti-tumor specificity of ACT. Among them, the ACT targeting mutant gene mutations, including ERBB2IP, KRAS and TP53, as well as those derived from viruses such as Epstein-Barr virus (EBV) and human papillomavirus (HPV), is primarily summarized. Moreover, the existing issues of neoantigen-specific ACT and corresponding countermeasures are summarized and discussed.

Objective:To analyze the clinicopathological characteristics and prognostic factors in gastric cancer patients with bone metastasis,and to evaluate the impact of different treatment regimens on survival in patients with synchronous and metachronous bone metastasis.Methods:A total of 120 gastric cancer patients with bone metastasis treated at Nanjing Drum Tower Hospital between 2015 and 2023 were enrolled,including 36 with synchronous bone metastasis and 84 with metachronous bone metastasis.Clinicopathological features were compared between the two groups using the χ2 test.Cox proportional hazards regression model was employed to identify risk factors for overall survival after bone metastasis(OS-BM).The Kaplan-Meier method was used to analyze the effects of different treatments on OS-BM in both synchronous and metachronous groups.Results:Among the 120 patients,104(86.6%)had metastases to other organs.Comparative analysis revealed that synchronous bone metastasis patients exhibited elevated serum C-reactive protein and decreased serum albumin,whereas metachronous bone metastasis patients had reduced peripheral white blood cell and neutrophil counts(all P<0.05).Metachronous bone metastasis(HR=2.35,95%CI[1.47,3.74],P<0.01),serum CA125≥30.2 U/mL(HR=1.6,95%CI[1.03,2.48],P=0.036),white blood cell count≥9.5×10?/L(HR=2.15,95%CI[1.17,3.92],P=0.013),and absence of immunotherapy(HR=2.26,95%CI[1.5,3.39],P<0.01)were independent risk factors affecting patient prognosis.Combined immunotherapy significantly prolonged OS-BM in gastric cancer patients with bone metastasis compared to non-immunotherapy regimens(9.63 vs 4.53 months,P=0.002).Patients with metachronous bone metastasis demonstrated better response to immunotherapy compared to those with synchronous metastases(median OS-BM:10.8 vs 7.3 months,P=0.004).Conclusion:Immunotherapy is an independent protective factor for survival in gastric cancer patients with bone metastasis.Early combination therapy centered on immunotherapy alongside chemotherapy is recommended to prolong survival in such patients.

Objective:To identify HLA-G-binding proteins(HGBPs)by screening targeting ankyrin sequences from a phage display-based ankyrin protein library using human leukocyte antigen G(HLA-G)as the target,and to evaluate their functions.Methods:The expression of HLA-G in tumor tissues and its correlation with clinical prognosis and immune infiltration were analyzed using bioinformatics tools such as TCGA and GTEx databses.The extracellular domain of HLA-G was subjected to biopanning with a phage-displayed ankyrin protein library,followed by random selection and sequencing of monoclonal phage clones.The functional properties of dominant phage clones were validated using ELISA and immunofluorescence staining.HGBPs were produced and purified using a prokaryotic expression system,and their affinity and tumor-specific binding ability were evaluated using ELISA,surface plasmon resonance(SPR),and immunofluorescence staining.Results:Bioinformatics analysis revealed that HLA-G is widely overexpressed in tumor tissues and is correlated with overall survival(OS)and immune cell infiltration(P<0.05).After five rounds of biopanning,dominant clones were obtained.Both ELISA and immunofluorescence staining results showed that these dominant phages had a significantly higher affinity to HLA-G positive cells compared to HLA-G negative cells(P<0.05,P<0.001).The purified HGBPs exhibited an affinity of up to 17 nmol/L for HLA-G.ELISA results showed significant binding of HGBP to HLA-G(P<0.05),and immunofluorescence staining confirmed that HGBP could specifically bind to HLA-G-positive cells(P<0.01).Conclusion:The HGBPs identified via phage display exhibit high affinity and specificity to HLA-G on tumor cells.

Objective:To evaluate the efficacy and safety of radiotherapy as a combined mode with in-situ vaccine for patients with advanced soft tissue sarcoma(STS).Methods:The clinical data of 12 patients with advanced STS who received combination therapy mode at the Cancer Center of Gulou Hospital Affiliated to the School of Medicine of Nanjing University between December 2020 and September 2024 were retrospectively analyzed.All 12 patients received combined therapy.The main radiotherapeutic approach was hypofractionated radiotherapy.The targeted therapy mainly involved Anlotinib(in 10 cases)or Apatinib(in 2 cases).Immunotherapy mainly involved PD-1 antibodies.The primary endpoint was disease control rate(DCR),and the secondary endpoints were objective response rate(ORR)and safety.Results:Among the 12 STS patients who received combined treatment,0 cases achieved CR,4 cases achieved PR;7 cases had SD,and 1 case had PD.The ORR was 33%,and the DCR was 91.7%,among which the DCR of the target lesions was 100%.Among the 12 patients,9 patients experienced grade Ⅰ to grade Ⅱ adverse reactions.The most frequently occurring hematological adverse reactions were anemia(6 cases)and abnormal results of liver function tests(3 cases).The most frequently occurring non-hematological adverse reactions were proteinuria(5 cases),hypertension(4 cases),abnormal thyroid function(3 cases),anorexia(3 cases),and nausea and vomiting(2 cases).Only 2 cases had grade Ⅲ hematological toxicity,and 1 case had grade Ⅲpneumothorax.Conclusion:Radiotherapy as a combined therapy mode with in situ vaccine can achieve a higher DCR in advanced soft tissue sarcomas without serious adverse reactions.This combined treatment modality demonstrates good efficacy and safety.