scholarly journals Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: A Systematic Review

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5218
Author(s):  
Walid Shalata ◽  
Amjad Abu-salman ◽  
Rachel Steckbeck ◽  
Binil Mathew Jacob ◽  
Ismaell Massalha ◽  
...  
Keyword(s):  
Systematic Review ◽  
T Cells ◽  
Mortality Rate ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cardiac Toxicity ◽  
Checkpoint Inhibitors ◽  
Conduction Disorders ◽  
Stimulation Of

Immune checkpoint inhibitors are immune stimulatory drugs used to treat many types of cancer. These drugs are antibodies against inhibitory proteins, such as CTLA-4 and PD-1/PD-L1, that are expressed on immune cells. When bound, they allow for increased stimulation of T cells to fight tumor cells. However, immune checkpoint inhibitors have several immune-related adverse effects. Many cases have come to light recently of cardiotoxicity as a result of treatment with these drugs. Cardiotoxicity from immune checkpoint inhibitors is unique due to its rarity and high mortality rate. Patients with this toxicity may present with myocarditis, pericarditis, Takotsubo cardiomyopathy, conduction disorders, and others within just a few weeks of starting immune checkpoint inhibitors. We present here a review of the current research on immune checkpoint inhibitors, their associated cardiotoxicities, the timing of presentation of these conditions, lab tests and histology for each condition, and finally the treatment of patients with cardiotoxicity. We observe a positive skew in the onset of presentation, which is significant for the treating physician.

scholarly journals Modulation of Determinant Factors to Improve Therapeutic Combinations with Immune Checkpoint Inhibitors

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1727
Author(s):  
Magalie Dosset ◽  
Elodie Lauret-Marie Joseph ◽  
Thaiz Rivera Vargas ◽  
Lionel Apetoh
Keyword(s):  
T Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Memory T Cells ◽  
Checkpoint Inhibitors ◽  
Full Potential ◽  
Combined Treatments ◽  
Tumor Bed ◽  
Tumor Protection ◽  
Stimulation Of

Immune checkpoint inhibitors (ICPi) have shown their superiority over conventional therapies to treat some cancers. ICPi are effective against immunogenic tumors. However, patients with tumors poorly infiltrated with immune cells do not respond to ICPi. Combining ICPi with other anticancer therapies such as chemotherapy, radiation, or vaccines, which can stimulate the immune system and recruit antitumor T cells into the tumor bed, may be a relevant strategy to increase the proportion of responding patients. Such an approach still raises the following questions: What are the immunological features modulated by immunogenic therapies that can be critical to ensure not only immediate but also long-lasting tumor protection? How must the combined treatments be administered to the patients to harness their full potential while limiting adverse immunological events? Here, we address these points by reviewing how immunogenic anticancer therapies can provide novel therapeutic opportunities upon combination with ICPi. We discuss their ability to create a permissive tumor microenvironment through the generation of inflamed tumors and stimulation of memory T cells such as resident (TRM) and stem-cell like (TSCM) cells. We eventually underscore the importance of sequence, dose, and duration of the combined anticancer therapies to design optimal and successful cancer immunotherapy strategies.

Immune checkpoint and checkpoint inhibitors in hepatocellular carcinoma

2018 ◽  
Vol 1 (1) ◽  
pp. 28-32
Author(s):  
Piyawat Komolmit
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell Receptor ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cell Receptor ◽  
Immune Checkpoints ◽  
Histocompatibility Complex

การรักษามะเร็งด้วยแนวความคิดของการกระตุ้นให้ภูมิต้านทานของร่างกายไปทำลายเซลล์มะเร็งนั้น ปัจจุบันได้รับการพิสูจน์ชัดว่าวิธีการนี้สามารถหยุดยั้งการแพร่กระจายของเซลล์มะเร็ง โดยไม่ก่อให้เกิดภาวะแทรกซ้อนทางปฏิกิริยาภูมิต้านทานต่ออวัยวะส่วนอื่นที่รุนแรง สามารถนำมาใช้ทางคลินิกได้ ยุคของการรักษามะเร็งกำลังเปลี่ยนจากยุคของยาเคมีบำบัดเข้าสู่การรักษาด้วยภูมิต้านทาน หรือ immunotherapy ยากลุ่ม Immune checkpoint inhibitors โดยเฉพาะ PD-1 กับ CTLA-4 inhibitors จะเข้ามามีบทบาทในการรักษามะเร็งตับในระยะเวลาอันใกล้ จำเป็นแพทย์จะต้องมีความรู้ความเข้าใจในพื้นฐานของ immune checkpoints และยาที่ไปยับยั้งโมเลกุลเหล่านี้ Figure 1 เมื่อ T cells รับรู้แอนทิเจนผ่านทาง TCR/MHC จะมีปฏิกิริยาระหว่าง co-receptors หรือ immune checkpoints กับ ligands บน APCs หรือ เซลล์มะเร็ง ทั้งแบบกระตุ้น (co-stimulation) หรือยับยั้ง (co-inhibition) TCR = T cell receptor, MHC = major histocompatibility complex

scholarly journals From Oncogenic Signaling Pathways to Single-Cell Sequencing of Immune Cells: Changing the Landscape of Cancer Immunotherapy

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2278
Author(s):  
Afshin Derakhshani ◽  
Zeinab Rostami ◽  
Hossein Safarpour ◽  
Mahdi Abdoli Shadbad ◽  
Niloufar Sadat Nourbakhsh ◽  
...  
Keyword(s):  
Single Cell ◽  
Signaling Pathways ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cancer Development ◽  
Immune Checkpoints ◽  
Single Cell Sequencing ◽  
Increased Risk

Over the past decade, there have been remarkable advances in understanding the signaling pathways involved in cancer development. It is well-established that cancer is caused by the dysregulation of cellular pathways involved in proliferation, cell cycle, apoptosis, cell metabolism, migration, cell polarity, and differentiation. Besides, growing evidence indicates that extracellular matrix signaling, cell surface proteoglycans, and angiogenesis can contribute to cancer development. Given the genetic instability and vast intra-tumoral heterogeneity revealed by the single-cell sequencing of tumoral cells, the current approaches cannot eliminate the mutating cancer cells. Besides, the polyclonal expansion of tumor-infiltrated lymphocytes in response to tumoral neoantigens cannot elicit anti-tumoral immune responses due to the immunosuppressive tumor microenvironment. Nevertheless, the data from the single-cell sequencing of immune cells can provide valuable insights regarding the expression of inhibitory immune checkpoints/related signaling factors in immune cells, which can be used to select immune checkpoint inhibitors and adjust their dosage. Indeed, the integration of the data obtained from the single-cell sequencing of immune cells with immune checkpoint inhibitors can increase the response rate of immune checkpoint inhibitors, decrease the immune-related adverse events, and facilitate tumoral cell elimination. This study aims to review key pathways involved in tumor development and shed light on single-cell sequencing. It also intends to address the shortcomings of immune checkpoint inhibitors, i.e., their varied response rates among cancer patients and increased risk of autoimmunity development, via applying the data from the single-cell sequencing of immune cells.

How can we manage the cardiac toxicity of immune checkpoint inhibitors?

2021 ◽  
Author(s):  
Remo Poto ◽  
Giancarlo Marone ◽  
Flora Pirozzi ◽  
Maria Rosaria Galdiero ◽  
Alessandra Cuomo ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cardiac Toxicity ◽  
Checkpoint Inhibitors

scholarly journals Inhibition of the PI3K/mTOR Pathway in Breast Cancer to Enhance Response to Immune Checkpoint Inhibitors in Breast Cancer

2021 ◽  
Vol 22 (10) ◽  
pp. 5207
Author(s):  
Chi Yan ◽  
Jinming Yang ◽  
Nabil Saleh ◽  
Sheau-Chiann Chen ◽  
Gregory D. Ayers ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Tumor Growth ◽  
Cd8 T Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Mtor Pathway ◽  
Complete Regression ◽  
Mtor Inhibition

Objectives: Inhibition of the PI3K/mTOR pathway suppresses breast cancer (BC) growth, enhances anti-tumor immune responses, and works synergistically with immune checkpoint inhibitors (ICI). The objective here was to identify a subclass of PI3K inhibitors that, when combined with paclitaxel, is effective in enhancing response to ICI. Methods: C57BL/6 mice were orthotopically implanted with syngeneic luminal/triple-negative-like PyMT cells exhibiting high endogenous PI3K activity. Tumor growth in response to treatment with anti-PD-1 + anti-CTLA-4 (ICI), paclitaxel (PTX), and either the PI3Kα-specific inhibitor alpelisib, the pan-PI3K inhibitor copanlisib, or the broad spectrum PI3K/mTOR inhibitor gedatolisib was evaluated in reference to monotherapy or combinations of these therapies. Effects of these therapeutics on intratumoral immune populations were determined by multicolor FACS. Results: Treatment with alpelisib + PTX inhibited PyMT tumor growth and increased tumor-infiltrating granulocytes but did not significantly affect the number of tumor-infiltrating CD8+ T cells and did not synergize with ICI. Copanlisib + PTX + ICI significantly inhibited PyMT growth and increased activation of intratumoral CD8+ T cells as compared to ICI alone, yet did not inhibit tumor growth more than ICI alone. In contrast, gedatolisib + ICI resulted in significantly greater inhibition of tumor growth compared to ICI alone and induced durable dendritic-cell, CD8+ T-cell, and NK-cell responses. Adding PTX to this regimen yielded complete regression in 60% of tumors. Conclusion: PI3K/mTOR inhibition plus PTX heightens response to ICI and may provide a viable therapeutic approach for treatment of metastatic BC.

Cardiotoxicity of immune checkpoint inhibitors: A systematic review and meta-analysis of randomised clinical trials

2021 ◽  
Vol 148 ◽  
pp. 76-91
Author(s):  
Elisa Agostinetto ◽  
Daniel Eiger ◽  
Matteo Lambertini ◽  
Marcello Ceppi ◽  
Marco Bruzzone ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Randomised Clinical Trials
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