التفاصيل البيبلوغرافية
| العنوان: |
TGFβ2 Induces the Soluble Isoform of CTLA-4 – Implications for CTLA-4 Based Checkpoint Inhibitor Antibodies in Malignant Melanoma. |
| المؤلفون: |
Khanolkar, Rahul C., Zhang, Chu, Al-Fatyan, Farah, Lawson, Linda, Depasquale, Ivan, Meredith, Fiona M., Muller, Frank, Nicolson, Marianne, Dahal, Lekh Nath, Abu-Eid, Rasha, Rajpara, Sanjay, Barker, Robert Norman, Ormerod, Anthony D., Ward, Frank James |
| المصدر: |
Frontiers in Immunology; 1/5/2022, Vol. 12, p1-14, 14p |
| مصطلحات موضوعية: |
MELANOMA, CYTOTOXIC T lymphocyte-associated molecule-4, IMMUNOGLOBULINS, T cells, IMMUNE response, IPILIMUMAB |
| مستخلص: |
Malignant melanoma is an aggressive form of cancer, which can be treated with anti-CTLA-4 and anti-PD-1 checkpoint inhibitor antibodies but while anti-CTLA-4 antibodies have clear benefits for some patients with melanoma, productive responses are difficult to predict and often associated with serious immune related adverse events. Antibodies specific to CTLA-4 bind two major isoforms of CTLA-4 in humans, the receptor isoform and a second naturally secretable, soluble isoform - sCTLA-4. The primary aim here was to examine the effect of selectively blocking the function of sCTLA-4 on in vitro immune responses from volunteer healthy or melanoma patient PBMC samples. Addition of recombinant sCTLA-4 to healthy PBMC samples demonstrated sCTLA-4 to have immunosuppressive capacity comparable to recombinant CTLA4-Ig, partially reversible upon antibody blockade. Further, we identified a mechanistic relationship where melanoma patient TGFβ2 serum levels correlated with sCTLA-4 levels and provided the basis for a novel protocol to enhance sCTLA-4 production and secretion by T cells with TGFβ2. Finally, a comparison of selective antibody blockade of sCTLA-4 demonstrated that both healthy and melanoma patient effector cytokine responses can be significantly increased. Overall, the data support the notion that sCTLA-4 is a contributory factor in cancer immune evasion. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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