ObjectiveTo investigate feasibility, safety, and problems to be solved in treatment with programmed death receptor protein-1 (PD-1) monoclonal antibody for patients with recurrent liver cancer after liver transplantation (LT).MethodAll of the domestic and foreign cases reports about the application of PD-1 monoclonal antibody in the patients with recurrent liver cancer after the LT were analyzed and summarized.ResultsIn six patients with recurrent liver cancer after the LT who received the PD-1 monoclonal antibody, the acute graft rejections were observed in 3 patients, 2 patients had the progressive disease but there was no evidence of the graft rejection, 1 patient achieved the complete response and there was no evidence of graft rejection and no side effects.ConclusionsAt present, effect of PD-1 monoclonal antibody therapy is still not sure in patients with recurrent liver cancer after LT. If PD-1 monoclonal antibody is used off-label, close surveillance is needed to discovery possible acute graft rejection.
Objective To summarize the changes in the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) in the context of immunotherapy and their impact on treatment outcomes. MethodsA systematic review of recent studies on the TME of PDAC was carried out to analyze the immune properties, intercellular interactions, and biological functions of its cellular and non-cellular components, disclose the molecular mechanisms of immunotherapy affects on the TME, explore the advancements in targeted therapy and potential biomarkers, and analyze the challenges in clinical applications and their impacts on the quality of life of patients. ResultsThe TME of PDAC exhibits highly immunosuppressive and heterogeneous characteristics, rich in diverse cells (such as pancreatic cancer cells, stellate cells, cancer-associated fibroblasts, immune cells) and non-cellular components (such as extracellular matrix). Immunotherapy is capable of regulating the immune balance in the TME and enhancing the anti-tumor response. Despite the progress made in multiple immunotherapy strategies (such as immune checkpoint inhibitors, chimeric antigen receptor cell therapy), challenges such as difficulty in selecting targets, drug resistance, and side effects still persist. Meanwhile, potential biomarkers such as leukemia inhibitory factor offer new directions for individualized treatment. ConclusionsThe TME of PDAC undergoes continuous changes during immunotherapy. In the future, it is requisite to integrate new technologies to deeply explore targets and biomarkers, optimize multimodal precise treatment strategies, enhance the safety and efficacy of immunotherapy, and improve the prognosis of patients.
ObjectiveTo summarize advances in immunotherapy for gastric cancer.MethodThe relevant literatures about immunotherapy for gastric cancer in recent years were reviewed.ResultsRecently, the immunotherapy for the tumors mainly included the immune checkpoint blocking, tumor vaccine, and adoptive immunotherapy. There were many studies on the immune checkpoint blocking, mainly targeting the antibodies of programmed death receptor 1 (PD-1) and cytotoxic T-lymphocyte associated antigen 4 (CTLA-4). A series of studies had shown that the pembrolizumab was effective in the patients with advanced gastric cancer who expressed PD-1 ligand positive. The nivolumab had become the first immune checkpoint inhibitor approved for the treatment of advanced gastric cancer in Asia, and the patients with mismatch repair defects could benefit more from the PD-1 treatment. Although the CTLA-4 targeted immune checkpoint blocking therapy had been reported, some studies had found that the patients with advanced gastric cancer didn’t benefit from the treatment of CTLA-4 monoclonal antibody ipilimumab. The tumor vaccine therapy in the gastric cancer had been reported. Due to the high heterogeneity of tumor cells in the gastric cancer, the tumor vaccine efficacy of autoantibody was not stable, based on the high- throughput sequencing of neoantigens identification and screening process was complex, the vaccine preparation needed the longer period, how to individualized screening the neoantigen, and the selection of antigens that could effectively activate the T cells to recognize and kill the tumor cells still needed to be overcame.ConclusionsTumor immunotherapy has received worldwide attention. Anti-PD-1 and its ligand as representative immune checkpoint statin therapy in treatment of advanced gastric cancer has showed great potential, but at present there are still many problems need to be solved, such as number of applicable patients of immunotherapy is small, curative effect of immune checkpoint inhibitor screening index also is not clear, tumor vaccine and adoptive cell therapy are promising but there is lack of evidence from clinical research data, combined use of existing treatments and immunotherapy on curative effect still needs more clinical trials to explore.
31 case of advanced primary liver cancer were treated by using IL-2 and LAK cells in which 15 cases were combined with surgery (group A) and 16 cases were combined with chemotherpy (Group B). 7～14 months follow-up showed: In group A there was no recurence and metastasis, and the cell-mediated immunity was obviously improved. In group B, the average life time was more than 5.84 months, the tumor average diameter dicreased in 10 cases ,and the cee-mediated immunity was also improved. The role of immunotherapy combined with surgery or chemotherapy was discussed.
ObjectiveTo review the present situation of immune checkpoint inhibitors in treatment of advanced hepatocellular carcinoma (HCC), and discuss the advance of combined immunotherapy.MethodsThe relevant literatures on researches of immune checkpoint inhibitors in the treatment of advanced HCC were retrieved to make an review.ResultsImmunotherapy intervention had been becoming a novel and promising therapeutic approach for HCC, which could suppress the progression of aggressive tumor and could inhibit tumor recurrence and metastasis shown in some pre-clinical trials. Other studies had found that the combined strategy of specific immunotherapy and conventional therapies could significantly improve the clinical outcomes of HCC patients.ConclusionCombined immunotherapy can significantly improve the clinical outcomes of HCC and benefit more patients with advanced HCC.
Resectable non-small cell lung cancer (NSCLC) is prone to recurrence and metastasis after simple surgery. Although patients can benefit from preoperative neoadjuvant chemotherapy and postoperative adjuvant chemotherapy, the 5-year survival rate is not significantly improved. In recent years, with the rise of immunotherapy, NSCLC immunotherapy has gradually received attention. Many explorations have been made on resectable NSCLC immunotherapy, and satisfactory results have been obtained. With the release of multiple phase 3 research results, a new chapter in resectable NSCLC immunotherapy has officially opened. However, there are still many problems in the immunotherapy of resectable NSCLC. This article reviews the current relevant research and provides reference for clinical application.
Fungal infection is an important clinical problem for patients with immune deficiency or immunosuppression. With deadly fungus infection case increasing, the development of antifungal vaccine attracts the attention of researchers. Dendritic cell (DC) is the unique antigen presenting cell (APC) to trigger the antifungal immune reaction, and recent studies indicate that the targeted vaccination strategy based on DC have prospective antifungal potentials. In this paper, we review the antifungal immunity mechanism and recent development of the targeted DC antifungal strategy.
Objective To analyze and summarize advantages, disadvantages, and limitations of present imaging techniques in assessing efficacy of immunotherapy for patient with hepatocellular carcinoma in order to provide strong evidence for drug therapy evaluation and clinical decision-making for it. Method The relevant literatures about imaging evaluation of immunotherapy for hepatocellular carcinoma were collected to make a review, then analyze and summarize the value of different imaging techniques. Results The immunotherapy, characterized by the noninvasive, high specificity and good curative effect, had been playing an important role in the treatment of hepatocellular carcinoma in recent years. The imaging techniques currently used to assess the immunotherapy results of hepatocellular carinoma mainly included the CT, MRI, ultrasound, and nuclear medicine, which could be used to better evaluate the effectiveness of immunotherapy. It was very important for screening of the patients’ treatment options and judging of the survival and prognosis. The most of the evaluation indicators were based on the anatomic evaluation criteria and it had some certain limitations in evaluating the immunotherapy efficacy of patient with hepatocellular carcinoma. Conclusions As an emerging biological therapy, immunotherapy has gradually become a hotspot in diagnosis and treatment of hepatocellular carcinoma in future. Present imaging techniques and evaluation criteria have certain limitations. More multifunctional imaging indicators need to be improved and developed so as to provide strong evidence for drug therapy evaluation and clinical decision of patient with hepatocellular carcinoma.
Objective To investigate immunological therapeutic effect and safety of dendritic cells (DCs) combined with heat shock protein 70 (HSP70)-peptide complex (PC) derived from autogeneic hepatoma tissue. Methods Thirty patients with hepatocellular carcinoma from February 2010 to February 2015 in the Gaochun People’s Hospital of Nanjing and The Third Affiliated Hospital of Nantong University were studied, and subsequently were divided into an immunotherapy group (treated with HSP70-PC/DCs vaccine,n=15) and a chemotherapy group (n=15) according to the prescribed postoperative treatment methods. The levels of T lymphocyte subtypes were assayed by FACS. The toxicity adverse reactions, alpha-fetoprotein (AFP), CA19-9, hepatic tumor recurrence rate, survival rate, and KPS of two groups patients were evaluated and compared between these two groups. Results ① The values of CD3+, CD4+, CD4+/CD8+, and CD3CD56 had no significant differences between the immunotherapy group and the chemotherapy group before treatment (P>0.05), which in the immunotherapy group were significantly higher than those in the chemotherapy group after treatment (P<0.05), and which were significantly higher in the immunotherapy group after treatment as compared with the levels before treatment (P<0.05), and which had no significant differences in the chemotherapy group between after treatment and before treatment (P>0.05). ② Before treatment, the levels of AFP and CA19-9 had no significant differences between the immunotherapy group and the chemotherapy group (P>0.05), which in the immunotherapy group were significantly lower than those in the chemotherapy group after treatment (P<0.05). In the immunotherapy group, the levels of AFP and CA19-9 after treatment were significantly lower than those before treatment (t=2.564，P=0.021；t=2.011，P=0.041), which in the chemotherapy group before treatment were decreased as compared with the levels before treatment (t=2.221,P=0.036;t=2.487,P=0.066). ③ The patients treated with the HSP-PC/DCs vaccines was well tolerated and no obvious toxicity was appeared. ④ All the patients were followed up 5–19 months with median follow-up time of 9 months. The median survival time was 560 d and 436 d in the immunotherapy group and the chemotherapy group, respectively. After treatment, KPS score was significantly higher and recurrence rate was significantly lower in the immunotherapy group as compared with the chemotherapy group (P<0.05). The total survival had no significant difference between the immunotherapy group and the chemotherapy group (P>0.05). Conclusions The preliminary results of limited cases in this study show that HSP70-PC/DC vaccination is safe and effective in treatment of hepatocellular carcinoma, the pulsed DCs are effective in activating specific T-cell responses against hepatocellular carcinoma cells. HSP70-PC/DC vaccine might improve immunity and prevent postoperative recurrence of hepatocellular carcinoma.
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.