Pancreatic cancer (PC) is a highly malignant tumor of the digestive system and has a concealed onset with rapid progression. The majority of PC patients are diagnosed in the middle to late stages, and the effectiveness of traditional treatment methods for advanced pancreatic cancer is limited, which results in a poor prognosis. Immunotherapy, as a novel treatment strategy, aims to suppress tumor growth and metastasis by modulating and enhancing the human immune system. It has become a hot point in current cancer prevention and treatment. This article will elaborate on the newest advancements in immunotherapy for PC. Furthermore, we point out the major challenges of PC immunotherapy.
In recent years, immune checkpoint inhibitor therapy has changed the treatment of various malignant tumors. Immunotherapy for specific targets currently plays an important role in melanoma, lung cancer and other tumors. Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor. Although the treatments include surgery, chemotherapy and radiotherapy, the clinical efficacy is limited, and the prognosis of advanced patients is poor. With the application of monoclonal antibodies such as programmed death 1/programmed death ligand 1 and cytotoxic T-lymphocyte antigen 4, MPM patients have more treatment options. And compared with traditional chemotherapy, immunotherapy may have the effect of improving survival and shrinking tumors. This article will summarize the current clinical trials of immunotherapy in MPM, and explain the current application and progress of immunotherapy in MPM from both single-agent immunotherapy and combined immunotherapy.
Lung cancer is the most frequent cancer and the leading cause of cancer death all around the world. Anti-programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) therapies have significantly improved the outcomes of non-small cell lung cancer (NSCLC) patients in recent years. However, the objective response rate in non-screened patients is only about 20%. It is very important to screen out the potential patients suitable for immunotherapy. Immunohistochemical staining of tumor tissue biopsies with PD-L1 antibodies can predict the therapeutic response to immunotherapy to some extent, but it still has some limitations. Recently some clinical studies have shown that PD-L1 expression in circulating tumor cells (CTC-PD-L1) is a potential independent biomarker and may provide important information for immunotherapy in NSCLC. This article will review technology for CTC-PD-L1 detection and the predictive value of CTC-PD-L1 for immunotherapy in NSCLC and review the latest clinical research progress.
Objective To explore the predictive value of peripheral blood cells in the efficacy of neoadjuvant immunotherapy combined with chemotherapy for esophageal squamous cell carcinoma. Methods A retrospective study was conducted on patients with esophageal squamous cell carcinoma (clinical stages Ⅱ-Ⅳa) who underwent neoadjuvant immunotherapy combined with chemotherapy at the Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College from April 2020 to November 2023. According to whether the pathology was completely relieved after treatment, patients were divided into a pathological complete remission group and a pathological incomplete remission group. According to the CAP criteria for tumor pathological regression grading after neoadjuvant therapy, patients were divided into groups (TRG=0, 1 defined as good efficacy, TRG=2, 3 defined as poor efficacy). Results A total of 92 patients with esophageal squamous cell carcinoma were included, including 72 males and 20 females. The average age was 65.86±7.66 years. The complete remission of pathology was closely related to the number of lymphocytes in the blood before treatment (P=0.019). The AUC for predicting complete remission of esophageal squamous cell carcinoma after neoadjuvant immunotherapy combined with chemotherapy was 0.678, the maximum Yoden index was 0.328, and the optimal cutoff value was 1.845. The incidence of postoperative pulmonary infection in the group with incomplete pathological remission (25% vs. 5.6%, P=0.030) was higher than that in the group with complete pathological remission. According to the optimal cutoff value classification, there was a statistically significant difference (P<0.05) in the pathological N stage and pathological TNM stage between the two groups. The efficacy response was closely related to the number of red blood cells in the blood before treatment (P=0.009). The AUC for predicting TRG response after neoadjuvant immunotherapy combined with chemotherapy in esophageal squamous cell carcinoma was 0.669, the maximum Yoden index was 0.385, and the optimal cutoff value was 4.235. There were significant differences in postoperative pathological T staging (P=0.000), N staging (P=0.041), and TNM staging (P=0.000). According to the optimal cutoff value classification, there was a statistically significant difference in age (P=0.000) and hypertension (P=0.022) between the two groups. Conclusion Before neoadjuvant therapy, lymphocyte absolute value≥1.845 and red blood cell count<4.235 have good predictive effects on pathological complete remission and pathological response of esophageal squamous cell carcinoma after neoadjuvant immunotherapy combined with chemotherapy.
The development of immunotherapy has revolutionized the landscape of cancer treatment. Personalized neoantigen vaccines are attractive systemic immunotherapies that trigger specific T-cell responses against highly specific neoantigens, and activate and expand helper and cytotoxic T-lymphocytes to enhance anti-tumor immunity. Based on the rapid development of bioinformatics and the continuous update of sequencing technology, cancer immunotherapy with tumor neoantigens has made promising breakthroughs and progress. Researchers are exploring the value of neoantigen vaccines alone or in combination in different tumor types. We provide an overview of the complex process that is necessary to generate a personalized neoantigen vaccine, discuss the current status of clinical studies and application testing personalized neoantigen vaccines in patients with cancer and future perspectives on this novel, personalized approach to immunotherapy.
ObjectiveTo investigate the safety and clinical efficacy of dendritic cell (DC)-cytokine induced killer (CIK) cell adoptive immunotherapy combined with chemotherapy in patients with gastric cancer after radical gastrectomy.MethodsForty-eight patients with gastric cancer after the radical gastrectomy receiving the DC-CIK cell adoptive immunotherapy combined with XELOX or FOLFOX chemotherapy were enrolled as a study group in the First Hospital of Lanzhou University from January 2014 to January 2016. In addition, 48 patients with gastric cancer after the radical gastrectomy in the same period and only receiving XELOX or FOLFOX chemotherapy were collected as a control group. The CD3+, CD3+CD4+, CD3+CD8+, CD3–CD56+ (NK cell), and CD3+CD56+ (NKT cell), toxic reaction, quality of life were evaluated in both groups before and after the treatment, and the long term effect were compared in both groups.Results① There were no significant differences in the gender, age, clinical stage, etc. between the two groups (P>0.05). ② The CD3+, CD3+CD4+, CD3+CD8+, CD3–CD56+, and CD3+CD56+ cells in the peripheral blood had no significant changes between before and after treatment in the study group (P>0.05), which were decreased after the treatment in the control group as compared with before the treatment and were significantly lower than those in the study group (P<0.05). ③ The levels of CEA, CA19-9, and CA724 in the peripheral blood after the treatment in the study group and the control group were significantly lower than those before the treatment (P<0.05), which in the study group were significantly lower than those in the control group after the treatment (P<0.05). ④ The incidences of leukopenia, thrombocytopenia, and diarrhea in the study group were significantly lower than those in the control group (P<0.05). ⑤ Compared with before the treatment, the body function and emotional function after the treatment were significantly improved in the study group (P<0.05). And in the body function, emotion function, role function, cognitive function, and social function were significantly improved than those in the control group (P<0.05) after the treatment. ⑥ The progression-free survival in the study group was significantly better than that in the control group (P<0.05). There was no significant difference in the overall survival between the study group and the control group (P>0.05).ConclusionDC-CIK cell adoptive immunotherapy combined with chemotherapy could significantly improve immune status and quality of life of patients with gastric cancer after radical gastrectomy, reduce adverse effects of chemotherapy, improve long term effect, and prolong progression-free survival.
Objective To examine the association between programmed cell death ligand 1 (PD-L1) expression and venous thromboembolism (VTE) risk in lung cancer patients treated with immune checkpoint inhibitors (ICIs). Methods We enrolled adults with lung cancer who initiated ICIs between January 2018 and March 2022 at West China Hospital of Sichuan University. The included patients were divided into PD-L1 TPS<50% group and PD-L1 TPS≥50% group. Clinical outcomes including VTE, pulmonary embolism (PE), and deep venous thrombosis (DVT) were evaluated with cox regression models. Results Of the 519 lung cancer patients receiving ICIs finnaly analyzed (347 cases with PD-L1 TPS<50%; 172 cases with PD-L1 TPS≥50%), VTE developed in 48 cases (9.2%) during the 12-month follow-up, of which 41 cases (7.9%) had DVT, 4 cases (0.8%) had PE, and 3 cases (0.6%) had DVT and PE. A higher incidence of VTE was observed in TPS<50% group versus TPS≥50% group (P=0.026), whereas there was a trend toward an increased rate of DVT, which was not statistically significant (P=0.052). Significant differences in PE were not found (P=0.152). After multivariable adjustment, PD-L1 TPS<50%, ECOG PS≥2, chronic obstructive pulmonary disease, and VTE history were associated with an increased VTE risk (P<0.05). Conclusion VTE occurred in 9.2% of ICI-treated lung cancer patients. PD-L1 TPS<50% was associated with an increased risk of VTE, which should be identified, prevented and intervened early in clinical practice.
Objective To assess the effectiveness of dust mite sublingual immunotherapy (SLIT) for treating allergic rhinitis. Methods The randomized controlled trials (RCTs) about SLIT treating allergic rhinitis were collected in MEDLINE, EMbase, The Cochrane library (Issue 10, 2012), CNKI, VIP, WanFang Data and CBM from inception to October, 2012. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted the data, and assessed the quality, and then the meta-analysis was performed by using RevMan 5.1 software. Results A total of 8 RCTs involving 788 patients were included. The results of meta-analysis showed that, compared with the control group, SLIT showed no obvious difference in the total effective rate (RR=1.15, 95%CI 0.88 to 1.50, P=0.29), but it was superior in decreasing the scores of both nasal symptom (SMD= ?1.13, 95%CI ?2.07 to ?0.20, P=0.02) and drug intake (SMD= ?0.60, 95%CI ?1.06 to ?0.15, P=0.009). Conclusion SLIT can improve the symptoms of patients with allergic rhinitis, and it can also decrease the using frequency of antihistamine, beta-blocker and nasal spray steroids.
ObjectiveTo identify genes associated with resistance to programmed cell death protein 1 (PD-1) inhibitors in colorectal cancer and elucidate their underlying mechanisms using bioinformatics approaches. MethodsGenes expression datasets were downloaded from the Gene Expression Omnibus (GEO) database to screen hypoxia-related genes (HRGs) and differentially expressed genes (DEGs). The intersection of HRGs and DEGs was defined as hypoxia-related differentially expressed genes (HDGs). The gene expression data of patients with colorectal cancer from The Cancer Genome Atlas (TCGA) were analyzed using Pearson correlation to identify the PD-1-related genes, further the STRING analysis (minimum interaction score was greater than 0.7) and Cytoscape were subsequently employed to screen the key PD-1-related genes. The relation between the screened key PD-1-related genes and the prognosis of colorectal cancer patients was analyzed to screen out the target genes. The real-time fluorescence reverse transcription quantitative polymerase chain reaction was used to analyze the expression of the target genes in the cancer tissues and their corresponding adjacent tissues of 20 patients with colorectal cancer. The Kaplan-Meier Plotter database and the ROC Plotter database were used to analyze the relation between the high and low expression of the target genes and the prognosis in different patients. The significance level was set as α=0.05. ResultsA total of 651 HRGs and 329 DEGs were screened out. By taking the intersection of these two sets, 37 HDGs were obtained for subsequent analysis. Through Pearson correlation analysis, 25 key PD-1-related genes were screened out and 10 and 14 key PD-1-related genes were screened out by the MCC algorithm and the MCODE algorithm respectively. By taking the intersection of these three sets, 3 key PD-1-related genes were obtained, then survival analysis, the Aurora kinase A (AURKA) gene was finally screened out as the target gene. The expression level of the AURKA gene in the pan-cancer patients who responded to PD-1 inhibitor treatment was significantly higher than that in non-responders (P＜0.001), and was significantly lower in the six colorectal cancer cells treated with hypoxia than in six colorectal cancer cells treated with normoxia (P＜0.001). The AURKA expression in the colorectal cancer tissues was significantly higher than that in the corresponding adjacent colorectal tissues (P=0.008). The overall survival of pan-cancer patients with high AURKA expression was better than that of those with low AURKA expression [HR (95%CI)=0.67 (0.49, 0.93), P=0.015]. Among the colorectal cancer patients with MMR deficiency, the patients with low AURKA gene expression had worse overall survival [HR (95%CI)=2.596 (1.028, 6.332), P=0.043] and recurrence-free survival [HR (95%CI)=4.201 (1.092, 16.150), P=0.037] as compared with those with high AURKA gene expression. The low AURKA expression was associated with significantly worse overall survivals in the colorectal cancer patients harboring wild-type or mutant TP53, BRAF, and KRAS as compared with high AURKA expression (P＜0.05), while no statistically significant difference was found in the overall survival of the normal MMR patients between with high AURKA expression and low AURKA expression (P=0.307). ConclusionThe results of this bioinformatics analysis suggest that hypoxia down-regulated AURKA expression, and low AURKA expression is associated with worse prognosis in colorectal cancer patients, and worse reactivity and prognosis in patients treated with PD-1 inhibitors.
ObjectiveTo recognize the latest research progress of immunotherapy for advanced gastric cancer (AGC). MethodThe domestic and international literature on immunotherapy for AGC in recent years were retrieved and reviewed. ResultsThe immunotherapy for AGC mainly focused on immune checkpoint inhibitors (ICIs), cellular immunity, and antitumor vaccines. The most immunotherapy researched was ICIs, especially for programmed death protein-1 / programmed death protein ligand 1, cytotoxic T lymphocyte associated antigen 4, and lymphocyte activating gene 3. The cellular immunotherapy and tumor vaccine therapy were less relatively. Although immunotherapy alone did not have a particularly good effect, its therapeutic effect was not inferior to that of chemotherapy alone and the incidence of adverse reactions was lower. Moreover, most studies had concluded that the use of immunotherapy in combination with other therapy had shown a good clinical efficacy, especially in combination with anti-human epidermal growth factor receptor 2 antibody, and chimeric antigen receptor T cells targeting Claudin 18.2 site had promising results in the AGC. ConclusionsWith the development of immunotherapy research, the strategies of immunotherapy for AGC are also constantly improving. Precision medicine is important in the process of immunotherapy. Targeted screening suitable patients and adopting precise treatment can further benefit the survival of patients with AGC.