ObjectiveTo summarize the latest advances in copper and cuproptosis in the field of breast cancer, and to provide a reference for clinical treatment decisions. MethodThe literatures related to copper and cuproptosis in recent years were read and summarized, and the research progress on the role of copper in breast cancer, the application of cuproptosis in the diagnosis and treatment of breast cancer were reviewed. ResultsCuproptosiswas a novel form of programmed cell death, which occurred via direct binding of copper to lipoylated components of the tricarboxylic acid (TCA) cycle, this resulted in lipoylated protein aggregation and subsequent iron-sulfur cluster protein loss, leading to proteotoxic stress and ultimately cell death. Cuproptosis induced proliferation and migration of breast cancer cell , mediated personalized immunotherapy, and participated in endocrine and chemotherapeutic drug resistance. ConclusionExploring the mechanism of cuproptosis provides potential applications for subsequent immunotherapy, endocrine therapy, and chemotherapy for breast cancer, leading to new effective strategies for patients.
Non-small cell lung cancer (NSCLC) is one of the most common types of cancer in the world and is an important cause for cancer death. Although the application of immunotherapy in recent years has greatly improved the prognosis of NSCLC, there are still huge challenges in the treatment of NSCLC. The immune microenvironment plays an important role in the process of NSCLC development, infiltration and metastasis, and they can interact and influence each other, forming a vicious circle. Notably, single-cell RNA sequencing enables high-resolution analysis of individual cells and is of great value in revealing cell types, cell evolution trajectories, molecular mechanisms of cell differentiation, and intercellular regulation within the immune microenvironment. Single-cell RNA sequencing is expected to uncover more promising immunotherapies. This article reviews the important researches and latest achievements of single-cell RNA sequencing in the immune microenvironment of NSCLC, and aims to explore the significance of applying single-cell RNA sequencing to analyze the immune microenvironment of NSCLC.
ObjectiveTo summarize the mechanism of action of programmed cell death protein 1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors, the application in breast cancer in recent years and the advances in the study of their bio-markers of effects. MethodRelevant literatures on PD-1/PD-L1 inhibitors and the study in the field of breast cancer were reviewed and summarized.ResultsIn recent years, the monotherapy of immune checkpoint inhibitors represented by PD-1/PD-L1 inhibitors or in combination with other therapies had brought new hope for patients with breast cancer especially triple-negative breast cancer (TNBC). However, only a small number of patients could benefit from breast cancer immunotherapy. The current researchers think that the efficacy of these drugs is related to PD-L1 expression in tumor tissue, tumor mutation burden (TMB), high level of microsatellite instability (MSI-H) and deficient mismatch repair (dMMR).ConclusionBreast cancer can benefit from the immunotherapy of PD-1/PD-L1 inhibitors, but formulating personalized medicine model, finding biomarkers that can predict efficacy and selecting patients with breast cancer who can benefit from it for targeted therapy are the new requirements in the new era of breast cancer immunotherapy.
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.
Neoadjuvant chemoradiotherapy or chemotherapy combined with surgery for locally advanced esophageal cancer has become the standard treatment, and despite the survival benefit, most patients still experience postoperative recurrence and distant metastasis. Immune checkpoint inhibitors play an anti-tumor role by activating T cells, and immunotherapy has become one of the important strategies for first-line and second-line treatment of advanced esophageal cancer with the continuous evolution of immunotherapy models. Regarding neoadjuvant immunotherapy for esophageal cancer, a large number of studies are being carried out and explored, which are expected to inject new vitality into neoadjuvant therapy for esophageal cancer. This article reviews the current clinical studies on neoadjuvant immunotherapy for esophageal cancer.
ObjectiveTo elucidate the latest research progress of Yes-associated protein (YAP) / transcriptional coactivator with PDZ-binding motif (TAZ) in regulating tumor drug resistance. MethodThe relevant literature on YAP/TAZ in regulating tumor cell chemotherapy, immunotherapy, and targeted therapy resistance was reviewed and summarized in the databases such as PubMed, CNKI, and so on. ResultsThe YAP/TAZ was involved in the resistance regulation of chemotherapy, immunotherapy, and targeted therapy in various human tumors. The YAP/TAZ could interact with various proteins to induce the occurrence of tumor resistance. The imbalance of YAP/TAZ signaling might lead to an important mechanism of tumor cell resistance. ConclusionsThere is a close relation between YAP/TAZ and tumor cell resistance. Studying the mechanism of YAP/TAZ regulating tumor resistance can provide new strategies and targets for addressing tumor resistance.
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.
Esophageal squamous cell carcinoma is the main histological type of esophageal cancer in China, which seriously threatens the health of people. The application of immunotherapy, mainly immune checkpoint inhibitors, has greatly improved the prognosis of patients with esophageal squamous cell carcinoma, but the efficacy of treatment is still limited. Tertiary lymphoid structure (TLS) is an ectopic organized lymphoid structure that accumulates in non-lymphoid organs. Previous studies have found that TLS in esophageal squamous cell carcinoma is associated with better patient outcomes and enhanced immunotherapy efficacy. Based on current researches about TLS in esophageal squamous cell carcinoma, this paper reviews the relationship between TLS and the prognosis and immunotherapy of patients. We hope to provide reference for the precise immunotherapy of esophageal squamous cell carcinoma.
With the publication of several phase Ⅱ and Ⅲ clinical studies, the multidisciplinary diagnostic and therapeutic strategies for early resectable non-small cell lung cancer (rNSCLC) are rapidly evolving. These studies have elucidated the significant effects of neoadjuvant and adjuvant therapies on improving the prognosis of rNSCLC patients, while also highlighting the urgent need to revise and refine corresponding treatment protocols and clinical pathways. In response, the International Association for the Study of Lung Cancer has assembled a diverse, multidisciplinary international expert panel to evaluate current clinical trials related to rNSCLC and to provide diagnostic, staging, and treatment recommendations for rNSCLC patients in accordance with the 8th edition of the AJCC-UICC staging system. The consensus recommendations titled "Neoadjuvant and adjuvant treatments for early stage resectable non-small cell lung cancer: Consensus recommendations from the International Associationfor the Study of Lung Cancer" outline 20 recommendations, 19 of which received over 85% agreement from the experts. The recommendations indicate that early rNSCLC patients should undergo evaluation by a multidisciplinary team and complete necessary imaging studies. For stage Ⅱ patients, consideration should be given to either adjuvant therapy following surgery or direct neoadjuvant/perioperative treatment, while stage Ⅲ patients are recommended to receive neoadjuvant chemoimmunotherapy followed by surgery. Postoperatively, adjuvant immunotherapy should be considered based on the expression levels of programmed cell death ligand 1, along with testing for other oncogenic driver mutations. For patients with epidermal growth factor receptor or anaplastic lymphoma kinase mutations sensitive to tyrosine kinase inhibitors, corresponding adjuvant targeted therapy is recommended. These recommendations aim to provide personalized and precise treatment strategies for early rNSCLC patients to enhance the efficacy of neoadjuvant and adjuvant therapies. This article provides an in-depth interpretation of these consensus recommendations.
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.