Facebook PixelPatient-specific genetic mutations dictate T cell-augmenting immunotherapy outcomes
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Patient-specific genetic mutations dictate T cell-augmenting immunotherapy outcomes

Image credit: Image created by Vijay_Ulaganathan (https://traps-vari.org/weblog/K/)

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ViJay K. U. Nathan; B.Pharm, M.Tech (BioEngg), PhD
ViJay K. U. Nathan; B.Pharm, M.Tech (BioEngg), PhD Feb 21, 2021
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(ii) Genetic mutations in PD-1 and CTLA-4 correlate with the activation state of circulating CD8 T cells

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Shubhankar Kulkarni
Shubhankar Kulkarni Feb 25, 2021

[1]Riley JL. PD-1 signaling in primary T cells. Immunol Rev. 2009;229(1):114-125. doi:10.1111/j.1600-065X.2009.00767.x

[2]Butte MJ, Keir ME, Phamduy TB, Sharpe AH, Freeman GJ. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity. 2007;27(1):111-122. doi:10.1016/j.immuni.2007.05.016

[3]Sharpe, A., Freeman, G. The B7–CD28 superfamily. Nat Rev Immunol 2, 116–126 (2002). https://doi.org/10.1038/nri727

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Shubhankar Kulkarni
Shubhankar Kulkarni2 days ago
Hi ViJay K. U. Nathan; B.Pharm, M.Tech (BioEngg), PhD ! Welcome 😄 . I admire your extensive research.

Here are a few questions and comments from my side:
1. Are SNPs in PD-1 and CTLA4 associated with malignancies in all subtypes of melanoma? - If we don't know the answer to this question, it might be a good option to start your research by answering this. It will help you eliminate those subtypes that are not affected by SNPs in PD-1 and CTLA4. You know that there also exist a large number of differences (in terms of the mutations) across the subtypes. This is one of the reasons we are moving towards personalized therapy for cancer patients. It will, therefore, be helpful if the affected subtypes are identified and studied separately.
2. You mentioned that only certain SNPs in PD-1 and CTLA4 are associated with anti-tumour CD8 T cell responses. Do we know which are these specific SNPs? If not, it makes sense to identify them as well. A reduced list of SNPs will be easier to perform a literature search (to answer questions (ii) and (iii) from your list).
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ViJay K. U. Nathan; B.Pharm, M.Tech (BioEngg), PhD
ViJay K. U. Nathan; B.Pharm, M.Tech (BioEngg), PhD2 days ago
Shubhankar Kulkarni Thank You Mr. Kulkarni !!

I appreciate your interest in this topic and I am happy to have your questions and comments.

Both the questions are excellent ones. Thank you very much.

We don't know the answers. It is absolutely worthwhile to find answers to these questions.

I am really looking forward to many such fascinating brainstorming questions and comments as yours.