scholarly journals The immunotherapy revolution in genitourinary malignancies

Immunotherapy ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 819-831
Author(s):  
Shruti U Gandhy ◽  
Ravi A Madan ◽  
Jeanny B Aragon-Ching
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Cell Cancer ◽  
Treatment Modalities ◽  
Metastatic Setting ◽  
Cancer Types ◽  
Therapeutic Cancer Vaccines ◽  
Demonstrate Survival Benefit

Immune checkpoint inhibitor (ICI) therapy and therapeutic cancer vaccines have continued to demonstrate survival benefit and durable clinical response in patients with renal cell cancer, prostate cancer and bladder cancer, with limited responses in testicular cancer. The role of immunotherapy in combination with chemotherapy or other targeted therapies in the neo-adjuvant, adjuvant and metastatic setting is actively being explored. We describe the current immunotherapy-related treatment modalities approved for genitourinary cancers, focusing on immune checkpoint inhibitors, vaccines and other modalities, and highlight ongoing studies involving immunotherapy in these cancer types.

scholarly journals Preexisting Autoimmune Disease: Implications for Immune Checkpoint Inhibitor Therapy in Solid Tumors

2019 ◽  
Vol 17 (6) ◽  
pp. 750-757 ◽  
Author(s):  
Laura C. Kennedy ◽  
Shailender Bhatia ◽  
John A. Thompson ◽  
Petros Grivas
Keyword(s):  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Solid Tumors ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Metastatic Setting ◽  
Checkpoint Inhibitor Therapy ◽  
Cancer Types

The use of immune checkpoint inhibitors (ICIs) is rapidly expanding to the treatment of many cancer types, both in the metastatic setting and as an adjuvant to other therapies. Clinical trials using ICIs have largely excluded patients with preexisting autoimmune diseases due to concerns for increased toxicity. However, emerging evidence shows that ICIs may be considered in some patients with autoimmunity. This review discusses the commonalities between clinical autoimmune diseases and ICI-induced immunotherapy-related adverse events, and summarizes the existing case series that describes patients with solid tumors who have a preexisting autoimmune disease. This review also discusses which patients with autoimmunity could be considered reasonable candidates for ICI therapy.

The emerging use of immune checkpoint blockade in the adjuvant setting for solid tumors: a review

Immunotherapy ◽  
2019 ◽  
Vol 11 (16) ◽  
pp. 1409-1422 ◽  
Author(s):  
Elissar Moujaess ◽  
Fady Gh Haddad ◽  
Roland Eid ◽  
Hampig Raphael Kourie
Keyword(s):  
Solid Tumors ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoint Blockade ◽  
Adjuvant Setting ◽  
Lung Cancers ◽  
Metastatic Setting ◽  
Postoperative Setting

The use of immune checkpoint inhibitors has been approved in the advanced and metastatic setting for many types of solid tumors. Nonetheless, their role in the adjuvant setting is limited to the treatment of surgically resected melanoma. Ipilimumab was the first immune checkpoint inhibitor approved for this indication, followed by nivolumab and pembrolizumab. Many ongoing trials are evaluating these molecules in the postoperative setting, alone or in combination with other therapies. Preliminary results are promising regarding the treatment of other cutaneous tumors, lung cancers, head and neck squamous cell carcinomas, bladder cancer and renal cell carcinomas. Some data assessing their use for the adjuvant treatment of esophageal, colorectal, ovarian cancer and other solid tumors are similarly emerging.

scholarly journals Immune Checkpoint Inhibitor Nephrotoxicity: Update 2020

Kidney360 ◽  
2020 ◽  
Vol 1 (2) ◽  
pp. 130-140 ◽  
Author(s):  
Shruti Gupta ◽  
Frank B. Cortazar ◽  
Leonardo V. Riella ◽  
David E. Leaf
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Solid Organ Transplantation ◽  
Treatment Strategies ◽  
Solid Organ ◽  
Diagnostic Uncertainty ◽  
Patients With Cancer ◽  
Underlying Malignancy

Immune checkpoint inhibitors (ICPIs) have transformed the landscape of oncology, but are associated with a variety of autoimmune adverse events, including AKI. ICPI-associated AKI (ICPI-AKI) is emerging as an increasingly frequent cause of AKI in patients with cancer, and poses unique diagnostic and management challenges to clinicians who care for these patients. In this review, we describe the incidence and risk factors for ICPI-AKI, including proton pump inhibitor use, CKD, and combination immunotherapy. We discuss the limitations of the various definitions used for ICPI-AKI in prior studies, and propose a novel classification system (definite, probable, and possible ICPI-AKI) that recognizes the diagnostic uncertainty inherent in many cases. We discuss the key clinicopathologic features and treatment strategies for ICPI-AKI, including the role of kidney biopsy versus empirical treatment with steroids. We also explore the under-studied area of ICPI use in the setting of solid organ transplantation, where nephrologists and oncologists must balance the risk of rejection versus treating the underlying malignancy. Finally, we summarize existing data on the role of ICPI rechallenge after an episode of ICPI-AKI.

Impact of the azoximer bromide concomitant therapy on patient outcomes in patients with melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21574-e21574
Author(s):  
Natalya Shendaleva ◽  
Aleksei Viktorovich Novik ◽  
Anton Zozulya ◽  
Tatyana Leonidovna Nekhaeva ◽  
Anna Semenova ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Treatment Modalities ◽  
Current Therapy ◽  
Metastatic Setting ◽  
Male Sex ◽  
The Impact

e21574 Background: Immunomodulators are used in the treatment of patients with melanoma. However, their role as anticancer therapeutic agents requires further investigation. Azoximer bromide (AB) is a well-tolerated immunomodulator that has been used in cases of melanoma. We investigated the impact of AB when used concomitantly with other melanoma treatment modalities on the overall survival (OS) and time to progression (TTP). Methods: We reviewed per protocol, a single-center real practice database that included 1,391 patients. Forty-two patients had received AB as a concomitant therapeutic agent. Concomitant medications included immune checkpoint inhibitors, cytokines, vaccines, targeted therapy and surgery alone in the adjuvant or metastatic setting. We built Cox proportional-hazards models for OS and TTP stratified by stage in SPSS v19. All known prognostic factors (LDH, TNM stage and sub-stage, mutations, sex, age, therapy by type, and by immunologic action) were included in the model along with AB therapy. Known factors were separated from unknown (AB therapy) by different variable blocks. A step forward method was used for model construction. Results: Significant (p < 0.05) factors to emerge in the OS model were LDH (Hazards ration [HR]: 1.458 for high LDH), sub-stage (HR: 1.718 for M1b-d sub-stage), BRAF mutation (HR: 0.698 if present), current therapy type (HR: 0.501 for immune checkpoint inhibitors (ICI), HR: 0.656 for targeted therapy (TT), HR: 1.275 for systemic immunotherapy, HR: 0.825 per added method for complex treatment, HR: 0.605 for surgery), previous treatment (HR: 0.778 for ICI, HR: 1.207 for single-agent chemotherapy, HR 1.176 for targeted or local treatment, HR: 1.315 for combination chemotherapy, HR: 2.039 for immunosuppressive factors reduction methods), male sex (HR: 1.204) and AB therapy (HR: 0.475). Significant factors in the TTP model were LDH (HR: 1.348 for high LDH), sub-stage (HR: 1.434 for B-D sub-stage), current therapy type (HR: 0.432 for (ICI), HR: 0.541 for TT, HR: 0.692 per added method for complex therapy HR: 0.705 for surgery), previous therapy (HR: 0.789 for ICI), male sex (HR: 1.167) and AB therapy (HR: 0.478). Conclusions: The addition of AB to standard therapy in melanoma appears to be an independent favorable prognostic factor. Prospective, randomized, clinical trials are needed to investigate these findings further.

scholarly journals Targeting nuclear acid-mediated immunity in cancer immune checkpoint inhibitor therapies

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Miaoqin Chen ◽  
Shiman Hu ◽  
Yiling Li ◽  
Ting Ting Jiang ◽  
Hongchuan Jin ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Cell Function ◽  
Checkpoint Inhibitors ◽  
Critical Role ◽  
Tumor Control ◽  
New Strategies

AbstractCancer immunotherapy especially immune checkpoint inhibition has achieved unprecedented successes in cancer treatment. However, there are many patients who failed to benefit from these therapies, highlighting the need for new combinations to increase the clinical efficacy of immune checkpoint inhibitors. In this review, we summarized the latest discoveries on the combination of nucleic acid-sensing immunity and immune checkpoint inhibitors in cancer immunotherapy. Given the critical role of nuclear acid-mediated immunity in maintaining the activation of T cell function, it seems that harnessing the nuclear acid-mediated immunity opens up new strategies to enhance the effect of immune checkpoint inhibitors for tumor control.

scholarly journals New emerging targets in cancer immunotherapy: the role of TIM3

ESMO Open ◽  
2019 ◽  
Vol 4 (Suppl 3) ◽  
pp. e000497 ◽  
Author(s):  
Alex Friedlaender ◽  
Alfredo Addeo ◽  
Giuseppe Banna
Keyword(s):  
Immune Checkpoint ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Lung Cancer Patients ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Cancer Types ◽  
Domain 3

Currently, the programmed death-1/programmed death ligand-1 and the cytotoxic T-lymphocyte-associated protein 4 are the two commonly targeted immune-checkpoint inhibition pathways. These drugs have significantly improved the prognosis of many cancer types. While immune-checkpoint inhibitors have revolutionised the treatment of many cancer types, the majority of patients still progress. Several treatment strategies have been pursued to improve current results. One approach is to combine two checkpoint inhibitors, currently with promising results in melanoma, renal cell carcinoma and a subset of non-small-cell lung cancer patients. The identification of new checkpoint targets could allow the field of immuno-oncology to evolve further. We will discuss one of the most promising immune-checkpoint targets currently under investigation, the T-cell immunoglobulin and mucin domain-3.

Immune Checkpoint Inhibitor-Related Pneumonitis

Respiration ◽  
2020 ◽  
pp. 1-11
Author(s):  
Georgia Gomatou ◽  
Vasilios Tzilas ◽  
Elias Kotteas ◽  
Konstantinos Syrigos ◽  
Demosthenes Bouros
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Epidemiological Data ◽  
Future Research ◽  
Organ Specific ◽  
Cancer Types

Immune checkpoint inhibitors are novel agents that have been proved efficacious in a variety of cancer types, but they are associated with a unique set of organ-specific, immune-related adverse events. Among them, immune-related pneumonitis requires special attention because it is difficult to diagnose and potentially lethal. Accumulating real-world epidemiological data suggest that immune-related pneumonitis is more frequent than previously reported. Its diagnosis requires exclusion of other causes and assessment of radiographic features on high-resolution CT of the chest. Management of immune-related pneumonitis is based on the use of immunosuppressants. Future research should be focused on finding predictive biomarkers for immune-related pneumonitis as well as optimizing its management.

scholarly journals Immuno-Metabolism: The Role of Cancer Niche in Immune Checkpoint Inhibitor Resistance

2021 ◽  
Vol 22 (3) ◽  
pp. 1258
Author(s):  
Chao-Yuan Weng ◽  
Cheng-Xiang Kao ◽  
Te-Sheng Chang ◽  
Yen-Hua Huang
Keyword(s):  
Immune Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Metabolic Reprogramming ◽  
Anti Cancer ◽  
Current Therapies ◽  
Inhibitor Resistance ◽  
Harsh Conditions

The use of immune checkpoint inhibitors (ICI) in treating cancer has revolutionized the approach to eradicate cancer cells by reactivating immune responses. However, only a subset of patients benefits from this treatment; the majority remains unresponsive or develops resistance to ICI therapy. Increasing evidence suggests that metabolic machinery in the tumor microenvironment (TME) plays a role in the development of ICI resistance. Within the TME, nutrients and oxygen are scarce, forcing immune cells to undergo metabolic reprogramming to adapt to harsh conditions. Cancer-induced metabolic deregulation in immune cells can attenuate their anti-cancer properties, but can also increase their immunosuppressive properties. Therefore, targeting metabolic pathways of immune cells in the TME may strengthen the efficacy of ICIs and prevent ICI resistance. In this review, we discuss the interactions of immune cells and metabolic alterations in the TME. We also discuss current therapies targeting cellular metabolism in combination with ICIs for the treatment of cancer, and provide possible mechanisms behind the cellular metabolic rewiring that may improve clinical outcomes.

scholarly journals What do Emergency Physicians Know About Immune Checkpoint Inhibitor-Related Toxicities: A Brief Report

2021 ◽  
Vol 14 (8) ◽  
Author(s):  
Thomas Butters ◽  
Wing Kin Liu ◽  
Michael Grant ◽  
Francesca Jackson-Spence ◽  
Ghufoor Zaynub ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Post Intervention ◽  
Chemotherapy Agent ◽  
Correct Score ◽  
Immune Mediated ◽  
Number Of Patients ◽  
Cancer Types

Background: Cancer types eligible for treatment with immune checkpoint inhibitors (ICI) have increased over the past decade thus simultaneously growing the number of patients presenting to emergency departments (ED) with immune mediated toxicities. Objectives: The objective of this study was to ascertain information regarding the knowledge and management of immune checkpoint inhibitor mediated toxicities amongst emergency department physicians. Methods: A multiple-choice questionnaire was developed assessing the understanding of ICI usage and management of immune mediated toxicities, amongst ED physicians in 6 major ED departments in London. Participating clinicians included all levels of trainees and ED physicians. Questionnaires were distributed during weekly ED educational sessions, followed by training on immune-mediated toxicities. Results: Between March 2019 and September 2019, the questionnaire was delivered to 126 participants (80% junior grade, 20% specialist ED consultants). There was no significant association between clinician's seniority and overall score reached on the questionnaire. Amongst all participants, 56, 49, and 36% identified correctly ICIs as the first-line treatment regimen for melanoma, renal cell carcinoma, and non-small cell lung cancer, respectively. Overall, 90% of the participants recognized correctly cisplatin as a chemotherapy agent and 77% pembrolizumab as an ICI agent. Generally, there was a good understanding of chemotherapy related toxicities, however, the participants scored less well on questions relating to ICIs. Ten months following the initial audit and educational intervention, a single site re-audit was performed. The total average correct score was similar pre- and post-intervention (8, 13%, respectively). Conclusions: Knowledge and management of immune mediated toxicities is inferior compared to chemotherapy across physicians working in major ED departments in London. This survey highlights the need for increased education on ICI amongst ED clinicians.

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