Development of Thrombocytopenia is Associated with Improved Survival in Patients Treated with Immunotherapy

Assi, Hussein; Asch, Adam S.; Machiorlatti, Michael; Vesely, Sara K.; Ibrahimi, Sami

doi:10.2144/fsoa-2020-0021

Cited by 14 publications

(13 citation statements)

References 24 publications

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“…One final provocative point is the observation of a potential correlation between irAE and improved clinical outcomes; 36 it has been posited that ir-TCP may be associated with improved clinical outcomes. 37 One of our patients (case 5) did indeed have an exceptional response to immunotherapy and remains in complete response from his metastatic colorectal cancer 18 months after the last cycle of pembrolizumab. In conclusion, ir-TCP is an uncommon entity which requires prompt recognition and individualized management in order to avoid interruption of therapy.…”

Section: Discussionmentioning

confidence: 73%

Immune thrombocytopenia after immune checkpoint inhibitor therapy

et al. 2021

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Section: Discussionmentioning

confidence: 73%

Immune thrombocytopenia after immune checkpoint inhibitor therapy

et al. 2021

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“…Although only a small proportion of cancer cells express PD‐L1 on their surface, a 2–4‐fold increase in the number of cancer cells expressing it, caused by platelets, likely reflects a highly significant effect size considering that metastasis is an extremely inefficient and selective process in which less than 0.01% of circulating cancer cells succeed 28,29 . In support of such a view is a recent study demonstrating that among urothelial carcinoma patients PD‐L1 positivity was associated with shorter metastasis‐free and overall survival in those with high platelet counts, 30 while another study of patients with metastatic malignancies treated with immune checkpoint inhibitors showed that a mild thrombocytopenia (grade 1; nadir platelet count 75–150 × 10 3 μl −1 blood) was associated with increased overall survival compared with non‐thrombocytopenic patients 31 . Using platelets derived from healthy donors we showed that platelets increase cancer cell PD‐L1 mRNA in addition to surface protein.…”

Section: Discussionmentioning

confidence: 92%

“…28,29 In support of such a view is a recent study demonstrating that among urothelial carcinoma patients PD-L1 positivity was associated with shorter metastasis-free and overall survival in those with high platelet counts, 30 while another study of patients with metastatic malignancies treated with immune checkpoint inhibitors showed that a mild thrombocytopenia (grade 1; nadir platelet count 75-150 × 10 3 μl −1 blood) was associated with increased overall survival compared with non-thrombocytopenic patients. 31 Using platelets derived from healthy donors we showed that platelets increase cancer cell PD-L1 mRNA in addition to surface protein.…”

Section: Discussionmentioning

confidence: 94%

Platelets stimulate programmed death‐ligand 1 expression by cancer cells: Inhibition by anti‐platelet drugs

Asgari

Lesyk

Poitras

et al. 2021

Journal of Thrombosis and Haemostasis

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Background: Platelets facilitate hematogenous metastasis in part by promoting cancer cell immunoevasion, although our understanding of platelet function in modulating the adaptive immune system in cancer is limited. A major negative regulator of the adaptive response is the immune checkpoint protein Programmed Death Ligand 1 (PD-L1).Objectives: As platelets secrete factors that may increase PD-L1 expression, we investigated whether they up-regulate cancer cell PD-L1, thus promoting immunoevasion, and whether common anti-platelet drugs inhibit this process.Methods: Platelets were isolated from human volunteers. A549 lung, PD-L1 null A549, and 786-O renal cancer cells were incubated with and without platelets, and cancer cell PD-L1 expression was measured by qPCR and flow cytometry. Additionally, platelet-cancer cell incubations were performed in the presence of common antiplatelet drugs, and with growth factor neutralizing antibodies. Following incubation with platelets, A549 were co-cultured with T-cells and interleukin-2 (IL-2) levels were measured by flow cytometry as a marker of T-cell activation.Results: Platelets increased PD-L1 mRNA and surface protein expression by A549 and 786-0 cells. Combined neutralization of VEGF and PDGF prevented the plateletinduced up-regulation of PD-L1 by A549, as did the anti-platelet drug eptifibatide.A549 incubated with platelets demonstrated a reduced ability to activate human T-cells, an effect reversed by eptifibatide. Conclusions:As platelets promote immunoevasion of the adaptive immune response by increasing cancer cell PD-L1 expression and as anti-platelet drugs prevent this immunoevasive response, the investigation of anti-platelet drugs as adjuvant therapy to immune checkpoint inhibitors may be warranted in the treatment of cancer.

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“…Generally, other irAEs have been shown to be associated with the efficacy of PD-1/PD-L1 inhibitors in patients with lung cancer ( 28 , 29 ). Same as other irAEs, grade 1 thrombocytopenia during ICIs therapy is positively associated with Overall survival (OS), but lacks of Progression-free survival (PFS) benefit ( 30 ). Immune thrombocytopenia usually is not fatal, but deaths caused by the adverse events had been reported in uncommon cases ( 25 ).…”

Section: Epidemiology Of Icis-induced Thrombocytopeniamentioning

confidence: 99%

Immune Thrombocytopenia Induced by Immune Checkpoint Inhibitrs in Lung Cancer: Case Report and Literature Review

Xie

Cao

2021

Front. Immunol.

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Immune checkpoint inhibitors (ICIs), including antibodies targeting programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1), are being extensively used on advanced human malignancies therapy. The treatment with ICIs have acquired durable tumor inhibition and changed the treatment landscape in lung cancer. Immune-related adverse events including pneumonitis and thyroiditis have been well described, but less frequent events, such as ICIs-induced thrombocytopenia, are now emerging and may sometimes be severe or fatal. Since early detection and prompt intervention are crucial to prevent fatal consequences, it is of outmost importance that medical staff is aware of these potential toxicities and learn to recognize and treat them adequately. This review focuses on the epidemiology, clinical presentation, mechanisms, and clinical management of ICIs-induced thrombocytopenia in patients with lung cancer. We also present a patient with advanced lung adenocarcinoma who received the PD-L1 inhibitor atezolizumab and eventually developed severe thrombocytopenia. The case indirectly suggests that cytokine changes might contribute to immune dysregulation in ICIs-induced thrombocytopenia.

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Development of Thrombocytopenia is Associated with Improved Survival in Patients Treated with Immunotherapy

Cited by 14 publications

References 24 publications

Immune thrombocytopenia after immune checkpoint inhibitor therapy

Immune thrombocytopenia after immune checkpoint inhibitor therapy

Platelets stimulate programmed death‐ligand 1 expression by cancer cells: Inhibition by anti‐platelet drugs

Immune Thrombocytopenia Induced by Immune Checkpoint Inhibitrs in Lung Cancer: Case Report and Literature Review

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