scholarly journals Overcoming malignant cell-based mechanisms of resistance to immune checkpoint blockade antibodies

2020 ◽  
Vol 65 ◽  
pp. 28-37 ◽  
Author(s):  
Reham Ajina ◽  
David J. Zahavi ◽  
Yong-Wei Zhang ◽  
Louis M. Weiner
Keyword(s):  
Immune Checkpoint ◽  
Malignant Cell ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Mechanisms Of Resistance ◽  
Immune Checkpoint Blockade Antibodies

Mechanisms of Resistance to Immune Checkpoint Blockade: Why Does Checkpoint Inhibitor Immunotherapy Not Work for All Patients?

2019 ◽  
pp. 147-164 ◽  
Author(s):  
Charlene M. Fares ◽  
Eliezer M. Van Allen ◽  
Charles G. Drake ◽  
James P. Allison ◽  
Siwen Hu-Lieskovan
Keyword(s):  
Immune Checkpoint ◽  
Acquired Resistance ◽  
Resistance Mechanisms ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Mechanisms Of Resistance ◽  
Primary Resistance ◽  
Wide Range ◽  
Clinical Responses ◽  
Tumor Types

The emergence of immune checkpoint blockade therapies over the last decade has transformed cancer treatment in a wide range of tumor types. Unprecedented and durable clinical responses in difficult-to-treat cancer histologies have been observed. However, despite these promising long-term responses, the majority of patients fail to respond to immune checkpoint blockade, demonstrating primary resistance. Additionally, many of those who initially respond to treatment eventually experience relapse secondary to acquired resistance. Both primary and acquired resistance are a result of complex and constantly evolving interactions between cancer cells and the immune system. Many mechanisms of resistance have been characterized to date, and more continue to be uncovered. By elucidating and targeting mechanisms of resistance, treatments can be tailored to improve clinical outcomes. This review will discuss the landscape of immune checkpoint blockade response data, different resistance mechanisms, and potential therapeutic strategies to overcome resistance.

scholarly journals Resistance to Immune Checkpoint Blockade in Uterine Leiomyosarcoma: What Can We Learn from Other Cancer Types?

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2040
Author(s):  
Wout De Wispelaere ◽  
Daniela Annibali ◽  
Sandra Tuyaerts ◽  
Diether Lambrechts ◽  
Frédéric Amant
Keyword(s):  
Immune Checkpoint ◽  
Gynecological Cancer ◽  
Single Agent ◽  
Acquired Resistance ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Clinical Activity ◽  
Uterine Leiomyosarcoma ◽  
Mechanisms Of Resistance ◽  
Cancer Types

The onset of immune checkpoint blockade (ICB) therapy over the last decade has transformed the therapeutic landscape in oncology. ICB has shown unprecedented clinical activity and durable responses in a variety of difficult-to-treat cancers. However, despite these promising long-term responses, a majority of patients fail to respond to single-agent therapy, demonstrating primary or acquired resistance. Uterine leiomyosarcoma (uLMS) is a rare high-risk gynecological cancer with very limited treatment options. Despite research indicating a strong potential for ICB in uLMS, a clinical trial assessing the response to immunotherapy with single-agent nivolumab in advanced-stage uLMS showed no clinical benefit. Many mechanisms of resistance to ICB have been characterized in a variety of tumor types, and many more continue to be uncovered. However, the mechanisms of resistance to ICB in uLMS remain largely unexplored. By elucidating and targeting mechanisms of resistance, treatments can be tailored to improve clinical outcomes. Therefore, in this review we will explore what is known about the immunosuppressive microenvironment of uLMS, link these data to possible resistance mechanisms extrapolated from other cancer types, and discuss potential therapeutic strategies to overcome resistance.

scholarly journals Mechanisms of Resistance to Immune Checkpoint Blockade

2018 ◽  
Vol 20 (1) ◽  
pp. 41-54 ◽  
Author(s):  
David Liu ◽  
Russell W. Jenkins ◽  
Ryan J. Sullivan
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Mechanisms Of Resistance

scholarly journals Tumor Genotype Is Shaping Immunophenotype and Responses to Immune Checkpoint Inhibitors in Solid Tumors

2020 ◽  
Vol 3 (3) ◽  
pp. 121-127
Author(s):  
Kathrina L. Marcelo-Lewis ◽  
Shhyam Moorthy ◽  
Ecaterina Ileana-Dumbrava
Keyword(s):  
Cell Death ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Mechanisms Of Resistance ◽  
Oncogenic Pathways ◽  
Immune Editing ◽  
Tumor Types

ABSTRACT A major breakthrough in cancer treatment was ushered in by the development of immune checkpoint blockade therapy such as anti-CTLA4 antibody and anti-PD-1 and anti-programmed cell death-ligand 1 antibodies that are now approved for use in an increasing number of malignancies. Despite the relative success of immune checkpoint inhibitors with certain tumor types, many patients still fail to respond to such therapies, and the field is actively trying to understand the mechanisms of resistance, intrinsic or acquired, to immune checkpoint blockade. Herein, we discuss the roles that somatic genomic mutations in oncogenic pathways play in immune editing, as well as some of the current approaches toward improving response to immunotherapy.

scholarly journals Implantable optical fibers for immunotherapeutics delivery and tumor impedance measurement

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ai Lin Chin ◽  
Shan Jiang ◽  
Eungyo Jang ◽  
Liqian Niu ◽  
Liwu Li ◽  
...  
Keyword(s):  
Optical Fibers ◽  
Immune Checkpoint ◽  
Impedance Measurement ◽  
Immune Checkpoint Blockade ◽  
Drug Dose ◽  
Checkpoint Blockade ◽  
Patient Response ◽  
Multiple Tumor ◽  
Delivery Strategies ◽  
Immune Checkpoint Blockade Antibodies

AbstractImmune checkpoint blockade antibodies have promising clinical applications but suffer from disadvantages such as severe toxicities and moderate patient–response rates. None of the current delivery strategies, including local administration aiming to avoid systemic toxicities, can sustainably supply drugs over the course of weeks; adjustment of drug dose, either to lower systemic toxicities or to augment therapeutic response, is not possible. Herein, we develop an implantable miniaturized device using electrode-embedded optical fibers with both local delivery and measurement capabilities over the course of a few weeks. The combination of local immune checkpoint blockade antibodies delivery via this device with photodynamic therapy elicits a sustained anti-tumor immunity in multiple tumor models. Our device uses tumor impedance measurement for timely presentation of treatment outcomes, and allows modifications to the delivered drugs and their concentrations, rendering this device potentially useful for on-demand delivery of potent immunotherapeutics without exacerbating toxicities.

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