Immune Checkpoint Inhibitors ; Transcriptome ; Immunotherapy ; Biomarkers, Tumor

Objective: This study aimed to explore the prevalence and associated factors of thyroid dysfunction among cancer patients treated with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). Methodology: A cross-sectional study was done in patients who received TKIs at Rajavithi Hospital in 2019. For patients treated with ICI, a retrospective chart review for patients seen in 2018 to 2019 was conducted. If there were abnormal thyroid function tests (TFT), thyroid autoantibodies were tested. Results: There were 144 patients on TKIs with a mean age of 56.0 years. Thyroid dysfunction was found in 14.6% of patients and most had subclinical hypothyroidism (n=16, 11.1%). Imatinib (n=11, 10.8%) and sunitinib (n=4, 100%) were the 2 most common TKIs given to patients with thyroid dysfunction. Thyroid dysfunction was associated with male sex, chronic kidney disease and hepatitis B virus infection but not with previous thyroid disease and presence of thyroid autoantibodies. There were 18 patients who received ICIs. The mean age was 63.3 years. Twelve patients (66.7%) used programmed cell death protein-1 antibody (anti-PD1), mainly nivolumab. Thyroid dysfunction was found in 50%, which occurred at a median duration of 46 days. Most patients had overt hypothyroidism and 55.6% needed levothyroxine replacement. Conclusion Thyroid dysfunctions from TKIs were mostly asymptomatic and mild in severity. Some types of TKIs might be associated with thyroid dysfunction. On the other hand, thyroid dysfunction from ICIs usually occurs within 6 months and requires levothyroxine replacement.
Tyrosine Kinase Inhibitors ; Immune Checkpoint Inhibitors ; Immunotherapy ; Neoplasms

The application of immune checkpoint inhibitors (ICIs) has shown impressive anti-tumor efficacy across multiple malignant tumors, leading to the prolonged survival period of tumor patients. However, immune-related adverse events should not be ignored. Checkpoint inhibitor pneumonitis (CIP) is a pulmonary adverse event that can occur in malignant tumor patients after receiving ICIs treatment. The incidence of CIP has been reported to range from 2.7% to 20.0% in clinical trials and real-world research. Furthermore, some patients might suffer from serious or fatal CIP, and the prognosis of such patients will be poor. Early detection, diagnosis and treatment may improve the prognosis of these patients. The establishment of a whole-process CIP comprehensive surveillance management mode covering the health care system and patients during ICIs treatment might be helpful to improve the early diagnosis and treatment capacity of CIP, which is a key measure to improve the prognosis of these patients.
Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Pneumonia ; Lung Neoplasms

The application of immune checkpoint inhibitors (ICIs) has shown impressive anti-tumor efficacy across multiple malignant tumors, leading to the prolonged survival period of tumor patients. However, immune-related adverse events should not be ignored. Checkpoint inhibitor pneumonitis (CIP) is a pulmonary adverse event that can occur in malignant tumor patients after receiving ICIs treatment. The incidence of CIP has been reported to range from 2.7% to 20.0% in clinical trials and real-world research. Furthermore, some patients might suffer from serious or fatal CIP, and the prognosis of such patients will be poor. Early detection, diagnosis and treatment may improve the prognosis of these patients. The establishment of a whole-process CIP comprehensive surveillance management mode covering the health care system and patients during ICIs treatment might be helpful to improve the early diagnosis and treatment capacity of CIP, which is a key measure to improve the prognosis of these patients.
Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Pneumonia ; Lung Neoplasms

Immune checkpoint inhibitors (ICIs) have demonstrated unparalleled clinical responses and revolutionized the paradigm of tumor treatment, while substantial patients remain unresponsive or develop resistance to ICIs as a single agent, which is traceable to cellular metabolic dysfunction. Although dysregulated metabolism has long been adjudged as a hallmark of tumor, it is now increasingly accepted that metabolic reprogramming is not exclusive to tumor cells but is also characteristic of immunocytes. Correspondingly, people used to pay more attention to the effect of tumor cell metabolism on immunocytes, but in practice immunocytes interact intimately with their own metabolic function in a way that has never been realized before during their activation and differentiation, which opens up a whole new frontier called immunometabolism. The metabolic intervention for tumor-infiltrating immunocytes could offer fresh opportunities to break the resistance and ameliorate existing ICI immunotherapy, whose crux might be to ascertain synergistic combinations of metabolic intervention with ICIs to reap synergic benefits and facilitate an adjusted anti-tumor immune response. Herein, we elaborate potential mechanisms underlying immunotherapy resistance from a novel dimension of metabolic reprogramming in diverse tumor-infiltrating immunocytes, and related metabolic intervention in the hope of offering a reference for targeting metabolic vulnerabilities to circumvent immunotherapeutic resistance.
Humans ; Neoplasms/pathology* ; Immunotherapy/methods* ; Immune Checkpoint Inhibitors/therapeutic use*

Combined immunotherapy based on immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma has achieved remarkable therapeutic effect in clinical research and practice. However, many problems that need to be resolved have also been recognized in the clinical promotion process. Therefore, the primary effort through the multidisciplinary experts' mutual discussion [Chinese multidisciplinary expert consensus on combined immunotherapy based on immune check point inhibitors for hepatocellular carcinoma (2021 version)] is to implement the principles and methods of clinical application of ICIs treatment, including the selection of indications, prescriptions, treatment methods, monitoring and management of treatment process and adverse reactions, and efficacy evaluation. In addition, the consensus aims to combine the latest research progress, summarize detailed clinical application rules and expert experience, so as to provide reference for health professionals.
Carcinoma, Hepatocellular/drug therapy* ; China ; Consensus ; Humans ; Immune Checkpoint Inhibitors ; Immunotherapy ; Liver Neoplasms/drug therapy*

Immunotherapy has recently led to a paradigm shift in cancer therapy, in which immune checkpoint inhibitors (ICIs) are the most successful agents approved for multiple advanced malignancies. However, given the nature of the non-specific activation of effector T cells, ICIs are remarkably associated with a substantial risk of immune-related adverse events (irAEs) in almost all organs or systems. Up to 90% of patients who received ICIs combination therapy experienced irAEs, of which majority were low-grade toxicity. Cytotoxic lymphocyte antigen-4 and programmed cell death protein-1/programmed cell death ligand 1 inhibitors usually display distinct features of irAEs. In this review, the mechanisms of action of ICIs and how they may cause irAEs are described. Some unsolved challenges, however really engrossing issues, such as the association between irAEs and cancer treatment response, tumor response to irAEs therapy, and ICIs in challenging populations, are comprehensively summarized.
Antineoplastic Agents/adverse effects* ; Humans ; Immune Checkpoint Inhibitors ; Immunotherapy/adverse effects* ; Neoplasms/drug therapy*

While immune checkpoint inhibitors(ICIs)are effective and promising treatments for a variety of malignancies,they also have safety concerns,especially the immune-related adverse events(irAEs).Unlike the side effects of traditional chemotherapy and targeted therapy,irAEs are adverse events caused by immune activation after ICIs treatment and thus may involve almost every system of the body.Therefore,biomarkers for predicting irAEs after ICIs treatment are urgently needed.Here we review the currently available predictive biomarkers of irAEs.
Biomarkers ; Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Immunotherapy/adverse effects* ; Neoplasms/drug therapy*

Renal cell carcinoma (RCC) is a common lethal urological cancer,the distant metastasis of which is the leading cause of death.Although targeted agents have remarkably improved the overall prognosis of RCC patients,nearly all the patients eventually acquire therapeutic resistance.With the advent of immune checkpoint inhibitors,immunotherapy based on tumor microenvironment (TME) has shown a broad scope in clinical application.The deepening understanding of TME leads to the changes of therapeutic strategies for advanced RCC,and the combination of targeted therapy and immunotherapy is exhibiting a promising prospect.Herein,we reviewed the TME characteristics,candidate predictive biomarkers,and possible targets for future development of drugs against RCC.
Carcinoma, Renal Cell/therapy* ; Female ; Humans ; Immune Checkpoint Inhibitors ; Immunotherapy ; Kidney Neoplasms/therapy* ; Male ; Tumor Microenvironment

Immune therapy has become the fourth approach after surgery, chemotherapy, and radiotherapy in cancer treatment. Many immune checkpoints were identified in the last decade since ipilimumab, which is the first immune checkpoint inhibitor to cytotoxic T-lymphocyte associated protein 4, had been approved by the US Food and Drug Administration (FDA) for the treatment of unresectable or metastatic melanoma in 2011. The use of several antibody drugs that target PD1/PD-L1 for various cancer treatments has been approved by the FDA. However, fewer people are benefitting from immune checkpoint inhibitor treatment in solid cancers. Approximately 80% of patients do not respond appropriately because of primary or acquired therapeutic resistance. Along with the characterization of more immune checkpoints, the combinatory treatment of multiimmune checkpoint inhibitors becomes a new option when monotherapy could not receive a good response. In this work, the author focuses on the combination therapy of multiple immune checkpoints (does not include targeted therapy of oncogenes or chemotherapy), introduces the current progression of multiple immune checkpoints and their related inhibitors, and discusses the advantages of combination therapy, as well as the risk of immune-related adverse events.
Combined Modality Therapy ; Humans ; Immune Checkpoint Inhibitors ; Immunotherapy ; Melanoma/drug therapy* ; Tumor Escape