scholarly journals Immunotherapy for Patients with Advanced Urothelial Cancer: Current Evidence and Future Perspectives

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Clizia Zichi ◽  
Marcello Tucci ◽  
Gianmarco Leone ◽  
Consuelo Buttigliero ◽  
Francesca Vignani ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Adaptive Immune Response ◽  
Tumor Infiltrating Lymphocytes ◽  
Invasive Disease ◽  
Current Evidence ◽  
Programmed Death

In recent years, immunotherapy has produced encouraging results in a rapidly increasing number of solid tumors. The responsiveness of bladder cancer to immunotherapy was first established in nonmuscle invasive disease in 1976 with intravesical instillations of bacillus Calmette-Guérin (BCG). Very recently immune checkpoint inhibitors demonstrated good activity and significant efficacy in metastatic disease. In particular the best results were obtained with programmed death-ligand-1 (PD-L1) and programmed death-1 (PD-1) inhibitors, but many other immune checkpoint inhibitors, including anti-cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) antibodies, are currently under investigation in several trials. Simultaneously other therapeutic strategies which recruit an adaptive immune response against tumoral antigens or employ externally manipulated tumor infiltrating lymphocytes might change the natural history of bladder cancer in the near future. This review describes the rationale for the use of immunotherapy in bladder cancer and discusses recent and ongoing clinical trials with checkpoint inhibitors and other novel immunotherapy agents.

scholarly journals Perioperative Systemic Treatment for Muscle-Invasive Bladder Cancer: Current Evidence and Future Perspectives

2021 ◽  
Vol 22 (13) ◽  
pp. 7201
Author(s):  
In-Ho Kim ◽  
Hyo-Jin Lee
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Systemic Treatment ◽  
Checkpoint Inhibitors ◽  
Invasive Bladder Cancer ◽  
Current Evidence ◽  
Future Perspectives ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Radical cystectomy is the primary treatment for muscle-invasive bladder cancer; however, approximately 50% of patients develop metastatic disease within 2 years of diagnosis, which results in dismal prognosis. Therefore, systemic treatment is important to improve the prognosis of muscle-invasive bladder cancer. Currently, several guidelines recommend cisplatin-based neoadjuvant chemotherapy before radical cystectomy, and adjuvant chemotherapy is recommended in patients who have not received neoadjuvant chemotherapy. Immune checkpoint inhibitors have recently become the standard treatment option for metastatic urothelial carcinoma. Owing to their clinical benefits, several immune checkpoint inhibitors, with or without other agents (including other immunotherapy, cytotoxic chemotherapy, and emerging agents such as antibody drug conjugates), are being extensively investigated in perioperative settings. Several studies for perioperative immunotherapy have shown that immune checkpoint inhibitors have promising efficacy with relatively low toxicity, and have explored the predictive molecular biomarkers. Herein, we review the current evidence and discuss the future perspectives of perioperative systemic treatment for muscle-invasive bladder cancer.

Urothelial carcinoma in the era of immune checkpoint inhibitors

Immunotherapy ◽  
2021 ◽  
Author(s):  
Nadine Khalife ◽  
Claude Chahine ◽  
Manal Kordahi ◽  
Tony Felefly ◽  
Hampig Raphael Kourie ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Urothelial Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Invasive Disease ◽  
Line Treatment ◽  
First Line ◽  
Metastatic Urothelial Carcinoma ◽  
Muscle Invasive

Bladder cancer is the seventh most frequent cancer worldwide. The majority of patients present with nonmuscle invasive disease, while 20% of the patients are diagnosed with muscle-invasive bladder cancer. The treatment of nonmuscle invasive disease is endoscopic resection followed by intravesical adjuvant treatment for high risk patients. The standard treatment of localized muscle-invasive disease is neoadjuvant chemotherapy followed by radical cystectomy. Platinum-based chemotherapy is the first-line treatment in locally advanced or metastatic urothelial carcinoma. Immune checkpoint inhibitors have been approved for the treatment of metastatic urothelial carcinoma as second-line treatment or first-line in platinum-ineligible patients. Recently, pembrolizumab have been approved in BCG-refractory nonmuscle invasive bladder cancer. This review summarizes the current evidence concerning immunotherapy in the treatment of urothelial carcinoma.

scholarly journals Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Current Progresses and Challenges

2021 ◽  
Vol 11 ◽  
Author(s):  
Hao-Tian Liu ◽  
Meng-Jie Jiang ◽  
Zhu-Jian Deng ◽  
Le Li ◽  
Jian-Li Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Research Progress ◽  
T Cell Signaling ◽  
Existing Problems ◽  
Programmed Death ◽  
New Treatment

Hepatocellular carcinoma (HCC) is one of the most common malignant tumor in the world and its incidence is increasing in many countries. In recent years, with the deepening understanding of the immune and pathological mechanisms of HCC, immunotherapy based on the regulation of tumor immune microenvironment has become a new treatment choice for patients with HCC. Immune checkpoint inhibitors (ICIs) targeting programmed death protein-1, programmed death protein-ligand-1, or cytotoxic T-lymphocyte-associated antigen 4 are the most widely used. Instead of general immune-enhancing therapies, ICIs can reactivate anti-tumor immune responses by disrupting co-inhibitory T cell signaling. In this review, the research progress and existing problems of ICIs in the treatment of HCC in recent years are reviewed.

scholarly journals PTEN Alterations as a Potential Mechanism for Tumor Cell Escape from PD-1/PD-L1 Inhibition

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1318 ◽  
Author(s):  
Cretella ◽  
Digiacomo ◽  
Giovannetti ◽  
Cavazzoni
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Tumor Infiltrating Lymphocytes ◽  
Suppressor Gene ◽  
Pten Expression ◽  
Advanced Cancer Patients ◽  
Pten Loss ◽  
Programmed Death

The recent approval of immune checkpoint inhibitors drastically changed the standard treatments in many advanced cancer patients, but molecular changes within the tumor can prevent the activity of immunotherapy drugs. Thus, the introduction of the inhibitors of the immune checkpoint programmed death-1/programmed death ligand-1 (PD-1/PD-L1), should prompt deeper studies on resistance mechanisms, which can be caused by oncogenic mutations detected in cancer cells. PTEN, a tumor suppressor gene, dephosphorylates the lipid signaling intermediate PIP3 with inhibition of AKT activity, one of the main effectors of the PI3K signaling axis. As a consequence of genetic or epigenetic aberrations, PTEN expression is often altered, with increased activation of PI3K axis. Interestingly, some data confirmed that loss of PTEN expression modified the pattern of cytokine secretion creating an immune-suppressive microenvironment with increase of immune cell populations that can promote tumor progression. Moreover, PTEN loss may be ascribed to reduction of tumor infiltrating lymphocytes (TILs), which can explain the absence of activity of immune checkpoint inhibitors. This review describes the role of PTEN loss as a mechanism responsible for resistance to anti PD-1/PD-L1 treatment. Moreover, combinatorial strategies between PD-1/PD-L1 inhibitors and PI3K/AKT targeting drugs are proposed as a new strategy to overcome resistance to immune checkpoint inhibition.

scholarly journals Research progress in immune checkpoint inhibitors for lung cancer in China

2021 ◽  
Vol 13 ◽  
pp. 175883592110298
Author(s):  
Jiadi Gan ◽  
Yihua Huang ◽  
Wenfeng Fang ◽  
Li Zhang
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Research Progress ◽  
First Line ◽  
Future Directions ◽  
Programmed Death ◽  
Cell Death Protein

Immune checkpoint inhibitors (ICIs) have come to play an increasingly prominent role in the treatment of lung cancer, and some are recommended as a first-line treatment for late-stage non-small-cell lung cancer, either as a monotherapy or in combination with chemotherapy. Accordingly, the indications of Food and Drug Administration-approved ICIs have increased. In this background, China has implemented various policies to encourage and accelerate the marketing of domestic and imported innovative antitumor drugs. Eight ICIs have been approved in China. Among these, four imported programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors have received approval for six indications, and one domestic PD-1 inhibitor has received approval for one indication for lung cancer in 2018. Numerous clinical trials of ICIs for lung cancer are underway in China. This review aims to summarize the recent advances and future directions of ICIs, including PD-1 inhibitors, PD-L1 inhibitors, cytotoxic T lymphocyte-associated antigen-4 inhibitors, bi-specific antibodies, and a novel inhibitor of T-cell immune-receptor with Ig and immunoreceptor tyrosine-based inhibitory motif domains in immunotherapies for lung cancer in China.

Enterocolitis due to immune checkpoint inhibitors: a systematic review

Gut ◽  
2018 ◽  
Vol 67 (11) ◽  
pp. 2056-2067 ◽  
Author(s):  
Emilie Soularue ◽  
Patricia Lepage ◽  
Jean Frederic Colombel ◽  
Clelia Coutzac ◽  
David Faleck ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Cell Activity ◽  
Clinical Manifestations ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Increased Susceptibility

Immune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and programmed death-1 (PD-1)/ligand are increasingly used to treat several types of cancer. These drugs enhance antitumour T-cell activity and therefore induce immune-related adverse effects (irAE), of which gastrointestinal (GI) irAE are among the most frequent and severe. This systematic literature review summarises the clinical manifestations, management and pathophysiology of GI irAE due to immune checkpoint inhibitors. GI irAE induced by anti-CTLA-4 are frequent, potentially severe and resemble IBD, whereas those induced by PD-1 blockade seem to be less frequent and clinically more diverse. Baseline symbiotic gut microbiota is associated with an enhanced antitumour response to immune checkpoint inhibitors and an increased susceptibility to developing enterocolitis, in patients treated with anti-CTLA-4. These findings open new perspectives for possible manipulation of the gut microbiota in order to better identify responders to immune checkpoint inhibitors and to increase their efficacy and safety.

Combining Radiotherapy with Immunocheckpoint Inhibitors or CAR-T in Renal Cell Carcinoma

2020 ◽  
Vol 21 (4) ◽  
pp. 416-423 ◽  
Author(s):  
Matteo Santoni ◽  
Daniel Y.C. Heng ◽  
Gaetano Aurilio ◽  
Andrea Iozzelli ◽  
Lucilla Servi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Second Life ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Programmed Death ◽  
Car T

Radiotherapy is considered a second life in Renal Cell Carcinoma (RCC) patients, mainly due to the introduction of immune checkpoint inhibitors, such as anti-Programmed-death (PD)-1, alone or in combination with anti-Cytotoxic T-Lymphocyte Antigen (CTLA)-4. Several trials are investigating the efficacy/safety of immune checkpoint inhibitors in sequential or combined strategies with radiotherapy. Chimeric Antigen Receptor (CAR)-T cells therapy as a promising approach in cancer patients has opened the way to novel possibilities of integrating therapies. The identification of biomarkers of tumor response to these combinations represents a challenge in RCC, together with the research for the best partner for immunotherapy in metastatic patients. In this review we illustrated preclinical/clinical data on the integration of radiotherapy with immunocheckpoint inhibitors or CART cells in RCC.

Current and Future Scenario of Immunotherapy for the Treatment of Hepatocellular Carcinoma

2020 ◽  
Vol 16 ◽  
Author(s):  
Shvetank Bhatt ◽  
Jovita Kanoujia ◽  
Arghya Kusum Dhar ◽  
Rakesh Kumar Singh ◽  
Jayaraman Rajangam
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Check Point ◽  
Programmed Death ◽  
Check Point Inhibitors ◽  
Cancer Types ◽  
Programed Cell Death

: The discovery of the immune checkpoint inhibitors such as programed cell death-1 protein/Programmed death ligand-1 or 2 and (PD-1/PD-L1 or PD-L2) and Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) paved the way for developing novel cancer treatment. The check point inhibitors are found to be very efficient in treating many hot tumors (with immune environment) such as bladder cancer, melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC) etc. Numerous clinical trials have been initiated to evaluate the safety and effectiveness of immune checkpoint inhibitors for patients with different cancer types, including hepatocellular carcinoma (HCC), pancreatic and prostate cancer. The results and findings of these trials are highly appreciated. However the search of check point inhibitors with better efficacy for the treatment of HCC is still going on. The present review focuses on advancement in HCC treatments with respect to various standard therapies and immunotherapy.

scholarly journals Immune checkpoint inhibitors-related myocarditis in patients with cancer: an analysis of international spontaneous reporting systems

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rulan Ma ◽  
Quanziang Wang ◽  
Deyu Meng ◽  
Kang Li ◽  
Yong Zhang
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Adverse Drug Events ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Reporting Odds Ratio ◽  
Real World Data ◽  
Safety Issues

Abstract Background Immune checkpoint inhibitors-induced myocarditis presents unique clinical challenges. Here, we assessed post-marketing safety of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed cell death-1 (PD-1), and programmed death-ligand 1 (PD-L1) inhibitors by mining the real-world data reported in two international pharmacovigilance databases. Methods We analyzed immune checkpoint inhibitors (ICIs)-associated fatal adverse drug events (ADEs) reports from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) collected from July 1, 2014 to December 31, 2019 and data from EudraVigilance (EV) database accessed on February 29, 2020. Three different data mining approaches were used to detect the signal of fatal myocarditis caused by ICIs. Results Based on 7613 ICIs-related ADEs reported to the EV database and 5786 ICIs-associated ADEs submitted to the FAERS database, the most frequently reported ADE was ipilimumab-related colitis. For myocarditis, nivolumab-associated myocarditis was the most common. Among the five fatal toxic effects associated with ICIs, the lethality rate of myocarditis was the highest. Therefore, we further analyzed ICI-associated myocarditis and found that elderly patients and male patients were more likely to develop ICIs-related myocarditis. The results of signal detection showed that the risk signal of avelumab-related myocarditis detected by reporting odds ratio (ROR) method and proportional reporting ratios (PRR) method was the highest, whereas the signal strength of ipilimumab-related myocarditis detected by Bayesian confidence propagation neural networks (BCPNN) method was the strongest. Conclusion The findings of this study indicated the potential safety issues of developing myocarditis when using ICIs, which were consistent with the results of previous clinical trials and could provide a reference for clinical workers when using ICIs.

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