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 compare the clinical efficacy and adverse events of chemoradiotherapy (CRT) combined with immunotherapy versus CRT alone in patients with locally recurrent esophageal squamous cell carcinoma (ESCC) after surgery.Methods:A total of 221 patients with postoperative locally recurrent ESCC who underwent CRT at the Affiliated Huai′an No. 1 People′s Hospital of Nanjing Medical University from January 2020 to December 2022 were retrospectively analyzed. Patients were divided into two groups according to treatment modality: the CRT group ( n=118) and the CRT plus immunotherapy group (combined group, n=103). Among the combined group, 39 patients received camrelizumab, 33 received sintilimab, and 31 received tislelizumab. Short-term efficacy, survival outcomes, and treatment-related adverse events were compared between the two groups. The Cox proportional hazards model was used to analyze prognostic factors for overall survival (OS). Results:No statistically significant differences were observed in baseline clinicopathological characteristics between the two groups. The objective response rate (ORR) in the combined group was 72.8%, significantly higher than 55.9% in the CRT group ( P=0.009). The 1- and 2-year OS rates in the CRT group were 68.6% and 41.5%, respectively, while the 1- and 2-year progression-free survival (PFS) rates were 56.8% and 30.5%, respectively. In the combined group, the 1- and 2-year OS rates were 84.5% and 55.3%, and the 1- and 2-year PFS rates were 67.0% and 42.7%, respectively. The differences in both OS and PFS between the two groups were statistically significant ( P=0.001 and 0.023, respectively). Multivariate analysis showed that Karnofsky performance status score of 70, TNM stage III, and CRT alone were independent risk factors for OS ( P=0.035, 0.031, and 0.002, respectively). The incidence of grade ≥3 adverse events did not differ significantly between the two groups ( P=0.550). A total of 85 grade 1-2 immune-related adverse events (irAEs) and 7 grade ≥3 irAEs occurred in 65 patients in the combined group. Subgroup analysis suggested that tislelizumab combined with CRT showed the most favorable efficacy and safety profile. Conclusion:For patients with locally recurrent ESCC after surgery, concurrent chemoradiotherapy combined with immunotherapy demonstrates promising efficacy with tolerable safety, and may offer a potential therapeutic advantage.

Objective:To compare the clinical efficacy and adverse events of chemoradiotherapy (CRT) combined with immunotherapy versus CRT alone in patients with locally recurrent esophageal squamous cell carcinoma (ESCC) after surgery.Methods:A total of 221 patients with postoperative locally recurrent ESCC who underwent CRT at the Affiliated Huai′an No. 1 People′s Hospital of Nanjing Medical University from January 2020 to December 2022 were retrospectively analyzed. Patients were divided into two groups according to treatment modality: the CRT group ( n=118) and the CRT plus immunotherapy group (combined group, n=103). Among the combined group, 39 patients received camrelizumab, 33 received sintilimab, and 31 received tislelizumab. Short-term efficacy, survival outcomes, and treatment-related adverse events were compared between the two groups. The Cox proportional hazards model was used to analyze prognostic factors for overall survival (OS). Results:No statistically significant differences were observed in baseline clinicopathological characteristics between the two groups. The objective response rate (ORR) in the combined group was 72.8%, significantly higher than 55.9% in the CRT group ( P=0.009). The 1- and 2-year OS rates in the CRT group were 68.6% and 41.5%, respectively, while the 1- and 2-year progression-free survival (PFS) rates were 56.8% and 30.5%, respectively. In the combined group, the 1- and 2-year OS rates were 84.5% and 55.3%, and the 1- and 2-year PFS rates were 67.0% and 42.7%, respectively. The differences in both OS and PFS between the two groups were statistically significant ( P=0.001 and 0.023, respectively). Multivariate analysis showed that Karnofsky performance status score of 70, TNM stage III, and CRT alone were independent risk factors for OS ( P=0.035, 0.031, and 0.002, respectively). The incidence of grade ≥3 adverse events did not differ significantly between the two groups ( P=0.550). A total of 85 grade 1-2 immune-related adverse events (irAEs) and 7 grade ≥3 irAEs occurred in 65 patients in the combined group. Subgroup analysis suggested that tislelizumab combined with CRT showed the most favorable efficacy and safety profile. Conclusion:For patients with locally recurrent ESCC after surgery, concurrent chemoradiotherapy combined with immunotherapy demonstrates promising efficacy with tolerable safety, and may offer a potential therapeutic advantage.

Waldenstrom's macroglobulinemia (WM) is a lymphoplasmacytic lymphoma associated with immunoglobulin M (IgM), due to its rarity in domestic and international reports, it is often overlooked in clinical treatment, and gradually progressing to end-stage renal disease and affecting patient's prognosis. In recent years, there has been an increase in treatment options for WM. This study reviewed the diagnosis and treatment of a patient with WM complicated by chronic renal failure, and analyzed the progress in diagnosis and treatment of this disease by reviewing relevant literatures from both domestic and international sources.

Objective:To detect gene mutations in a pedigree with dominant dystrophic epidermolysis bullosa (DDEB) .Methods:A 20-year-old male proband presented with repeated blisters, ulceration, pigmentation, scars on the limbs, and deformation of the nails/toenails after birth. There were 5 patients in the 3-generation family, and they all presented with typical skin lesions. Peripheral blood samples were obtained from 14 members of the pedigree (including the 5 patients) and 100 unrelated healthy controls. Whole-exome sequencing was performed in the proband to identify relevant mutation sites, which were then confirmed in the family by Sanger sequencing.Results:Genetic testing indicated that the proband and the other 4 patients all carried a missense mutation (c.7885G>A) in exon 107 of the COL7A1 gene, resulting in the substitution of glycine by arginine at amino acid position 2629 (p.G2629R). The mutation was identified neither in the 9 healthy relatives nor in the 100 unrelated healthy controls. The mutation co-segregated with DDEB in the family, and was not included in databases such as Pubmed, HGMD or ClinVar, suggesting it was a novel missense mutation. The amino acid encoded by this mutation may alter the structure of type Ⅶ collagen, thereby affecting its function.Conclusion:A novel missense mutation was identified in exon 107 of the COL7A1 gene in the family with DDEB, expanding the spectrum of mutations in the COL7A1 gene.

Objective To observe the value of intratumoral and peritumoral CT radiomics for evaluating KRAS gene status in patients with colorectal adenocarcinoma.Methods Totally 245 patients with colorectal adenocarcinoma were retrospectively enrolled and divided into mutant group(n=139)and wild group(n=106)according to KRAS gene status,also divided into training set(n=171)and test set(n=74)at a ratio of 7∶3.Clinical data were compared between groups,and clinical factors were screened with logistic regression analysis to establish a clinical model.Based on enhanced venous phase CT images,intratumoral volume of interest(VOI),peritumoral VOI,and intratumoral+peritumoral VOI were delineated,radiomics features were extracted,and radiomics models were constructed.The combination model was constructed based on the best radiomics model combined with clinical factors.The value of each model for evaluating KRAS gene status in patients with colorectal adenocarcinoma was analyzed.Results Significant differences of patients’gender and carcinoembryonic antigen(CEA)were found between mutant group and wild group(both P＜0.05),which were independent impact factors of KRAS gene status in patients with colorectal adenocarcinoma(both P＜0.05).The area under the curve(AUC)of clinical model for evaluating KRAS gene status in patients with colorectal adenocarcinoma in training set and test set was 0.633 and 0.658,respectively.Intratumoral+peritumoral 3 mm model was the best radiomics model,with AUC of 0.921 and 0.894 in training set and test set,respectively.AUC of the combination model in training set and test set was 0.949 and 0.956,respectively.In training set,significant differences of AUC were found between clinical model and intratumoral+peritumoral 3 mm model,also between clinical model and combination model(both P＜0.001),while in test set,significant differences of AUC were found between each two models(all P＜0.05).Conclusion Intratumoral+peritumoral 3 mm radiomics based on enhanced venous phase CT could help to evaluate KRAS gene status in patients with colorectal adenocarcinoma.Combining with patients’gender and CEA could further improve efficacy of this model.

Objective To observe the value of intratumoral and peritumoral CT radiomics combined with clinical features for preoperative predicting lymphovascular invasion(LVI)of early lung adenocarcinoma.Methods Totally 252 patients with stage Ⅰ-Ⅱa lung adenocarcinoma were retrospectively enrolled and were divided into positive group(n=63)and negative group(n=189)according to LVI or not,also into training set(n=201)and test set(n=51)at a ratio of 8∶2.Clinical data and CT findings being significantly different between groups were included in multivariate logistic regression analysis to screen independent predictors of early lung adenocarcinoma LVI and to construct CT-clinical model.The best radiomics features were extracted and screened in ROI of tumor(ROI1)and outward of 3(ROI2),5(ROI3)and 7 mm(ROI4)with automatic delineation and expanding algorithm,respectively.K-nearest neighbor(KNN),support vector machine(SVM),decision tree(DT),random forest(RF)and logistic regression(LR)algorithms were used to construct radiomics models.The best classifier algorithm and ROI which could provide more effective radiomics information were selected to construct the best radiomics model,which was used to construct the combined model combining with CT-clinical model.Receiver operating characteristic curves were drawn,and the areas under the curves(AUC)were calculated to evaluate the efficacy of the above models for preoperative predicting early lung adenocarcinoma LVI.Results Solid lesion and CT-N+stage were both independent risk factors for early lung adenocarcinoma LVI(both P＜0.05).Peritumor 5 mm volume(GTPV5)was obtained based on ROI3,and the best radiomics model was the model established based on 14 optimal radiomics feature selected from RFGTPV5.AUC of CT-clinical model,RFGPTV5 model and combined model for preoperative predicting early lung adenocarcinoma LVI was 0.875,0.908 and 0.917 in training set,while was 0.831,0.853 and 0.862 in test set,respectively.Conclusion Intratumoral and peritumoral CT radiomics combined with clinical features had good efficacy for preoperative predicting LVI of early lung adenocarcinoma.Intratumor and peritumor 5 mm ROI could provide more valuable information.