Home Newsletters Human Immunology News Alternative Splicing of the Inhibitory Immune Checkpoint Receptor SLAMF6 Generates a Dominant...

Alternative Splicing of the Inhibitory Immune Checkpoint Receptor SLAMF6 Generates a Dominant Positive Form, Boosting T Cell Effector Functions

0
Scientists showed that in humans, SLAMF6 has three splice isoforms involving its V-domain. Although the canonical receptor inhibited T-cell activation through SAP recruitment, the short isoform SLAMF6∆17-65 had a strong agonistic effect. T
[Cancer Immunology Research]
6445218 {6445218:2WIHK8C4} apa 50 1 160528 https://www.stemcellsciencenews.com/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3A%22zotpress-3d959299271ac3e2304ecbf2196371d4%22%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%222WIHK8C4%22%2C%22library%22%3A%7B%22id%22%3A6445218%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Hajaj%20et%20al.%22%2C%22parsedDate%22%3A%222021-01-01%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EHajaj%2C%20E.%2C%20Zisman%2C%20E.%2C%20Tzaban%2C%20S.%2C%20Merims%2C%20S.%2C%20Cohen%2C%20J.%2C%20Klein%2C%20S.%2C%20Frankenburg%2C%20S.%2C%20Sade-Feldman%2C%20M.%2C%20Tabach%2C%20Y.%2C%20Yizhak%2C%20K.%2C%20Navon%2C%20A.%2C%20Stepensky%2C%20P.%2C%20Hacohen%2C%20N.%2C%20Peretz%2C%20T.%2C%20Veillette%2C%20A.%2C%20Karni%2C%20R.%2C%20Eisenberg%2C%20G.%2C%20%26amp%3B%20Lotem%2C%20M.%20%282021%29.%20Alternative%20splicing%20of%20the%20inhibitory%20immune%20checkpoint%20receptor%20SLAMF6%20generates%20a%20dominant%20positive%20form%2C%20boosting%20T%20cell%20effector%20functions.%20%3Ci%3ECancer%20Immunology%20Research%3C%5C%2Fi%3E.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1158%5C%2F2326-6066.CIR-20-0800%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1158%5C%2F2326-6066.CIR-20-0800%3C%5C%2Fa%3E%20%3Ca%20title%3D%27Cite%20in%20RIS%20Format%27%20class%3D%27zp-CiteRIS%27%20href%3D%27https%3A%5C%2F%5C%2Fwww.stemcellsciencenews.com%5C%2Fwp-content%5C%2Fplugins%5C%2Fzotpress%5C%2Flib%5C%2Frequest%5C%2Frequest.cite.php%3Fapi_user_id%3D6445218%26amp%3Bitem_key%3D2WIHK8C4%27%3ECite%3C%5C%2Fa%3E%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Alternative%20splicing%20of%20the%20inhibitory%20immune%20checkpoint%20receptor%20SLAMF6%20generates%20a%20dominant%20positive%20form%2C%20boosting%20T%20cell%20effector%20functions%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Emma%22%2C%22lastName%22%3A%22Hajaj%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Elad%22%2C%22lastName%22%3A%22Zisman%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shay%22%2C%22lastName%22%3A%22Tzaban%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sharon%22%2C%22lastName%22%3A%22Merims%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jonathan%22%2C%22lastName%22%3A%22Cohen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shiri%22%2C%22lastName%22%3A%22Klein%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shoshana%22%2C%22lastName%22%3A%22Frankenburg%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Moshe%22%2C%22lastName%22%3A%22Sade-Feldman%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yuval%22%2C%22lastName%22%3A%22Tabach%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Keren%22%2C%22lastName%22%3A%22Yizhak%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ami%22%2C%22lastName%22%3A%22Navon%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Polina%22%2C%22lastName%22%3A%22Stepensky%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nir%22%2C%22lastName%22%3A%22Hacohen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Tamar%22%2C%22lastName%22%3A%22Peretz%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Andre%22%2C%22lastName%22%3A%22Veillette%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Rotem%22%2C%22lastName%22%3A%22Karni%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Galit%22%2C%22lastName%22%3A%22Eisenberg%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Michal%22%2C%22lastName%22%3A%22Lotem%22%7D%5D%2C%22abstractNote%22%3A%22SLAMF6%20is%20a%20homotypic%20receptor%20of%20the%20Ig-superfamily%20associated%20with%20progenitor%20exhausted%20T%20cells.%20Here%20we%20show%20that%20in%20humans%2C%20SLAMF6%20has%20three%20splice%20isoforms%20involving%20its%20V-domain.%20Although%20the%20canonical%20receptor%20inhibited%20T-cell%20activation%20through%20SAP%20recruitment%2C%20the%20short%20isoform%20SLAMF6%5Cu220617-65%20had%20a%20strong%20agonistic%20effect.%20The%20costimulatory%20action%20depended%20on%20protein%20phosphatase%20SHP-1%20and%20led%20to%20a%20cytotoxic%20molecular%20profile%20mediated%20by%20the%20expression%20of%20T-bet%20and%20Runx3.%20Patients%20treated%20with%20immune%20checkpoint%20blockade%20showed%20a%20shift%20toward%20SLAMF6%5Cu220617-65%20in%20peripheral%20blood%20T%20cells.%20We%20developed%20splice-switching%20antisense%20oligonucleotides%20%28ASOs%29%20designed%20to%20target%20the%20relevant%20SLAMF6%20splice%20junction.%20Our%20ASOs%20enhanced%20SLAMF6%5Cu220617-65%20expression%20in%20human%20tumor-infiltrating%20lymphocytes%2C%20and%20improved%20their%20capacity%20to%20inhibit%20human%20melanoma%20in%20mice.%20The%20Yin-Yang%20relationship%20of%20SLAMF6%20splice%20isoforms%20may%20represent%20a%20balancing%20mechanism%20that%20could%20be%20exploited%20to%20improve%20cancer%20immunotherapy.%22%2C%22date%22%3A%222021%5C%2F01%5C%2F01%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1158%5C%2F2326-6066.CIR-20-0800%22%2C%22ISSN%22%3A%222326-6066%2C%202326-6074%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fcancerimmunolres.aacrjournals.org%5C%2Fcontent%5C%2Fearly%5C%2F2021%5C%2F03%5C%2F24%5C%2F2326-6066.CIR-20-0800%22%2C%22collections%22%3A%5B%5D%2C%22dateModified%22%3A%222021-03-25T21%3A31%3A42Z%22%7D%7D%5D%7D
Hajaj, E., Zisman, E., Tzaban, S., Merims, S., Cohen, J., Klein, S., Frankenburg, S., Sade-Feldman, M., Tabach, Y., Yizhak, K., Navon, A., Stepensky, P., Hacohen, N., Peretz, T., Veillette, A., Karni, R., Eisenberg, G., & Lotem, M. (2021). Alternative splicing of the inhibitory immune checkpoint receptor SLAMF6 generates a dominant positive form, boosting T cell effector functions. Cancer Immunology Research. https://doi.org/10.1158/2326-6066.CIR-20-0800 Cite
Abstract
Exit mobile version