Home Newsletters Human Immunology News Combined Inhibition of SHP2 and CXCR1/2 Promotes Anti-Tumor T Cell Response in...

Combined Inhibition of SHP2 and CXCR1/2 Promotes Anti-Tumor T Cell Response in NSCLC

0
The authors found that SHP2 inhibitor treatment depleted alveolar and M2-like macrophages, induced tumor-intrinsic CCL5/CXCL10 secretion and promoted B and T lymphocyte infiltration in Kras- and Egfr-mutant non-small cell lung cancer.
[Cancer Discovery]
6445218 {6445218:3GSEF3RD} apa 50 1 165509 https://www.stemcellsciencenews.com/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3A%22zotpress-f466884cf38f234a767a45615aceb965%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%223GSEF3RD%22%2C%22library%22%3A%7B%22id%22%3A6445218%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Tang%20et%20al.%22%2C%22parsedDate%22%3A%222021-01-01%22%2C%22numChildren%22%3A3%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%3ETang%2C%20K.%20H.%2C%20Li%2C%20S.%2C%20Khodadadi-Jamayran%2C%20A.%2C%20Jen%2C%20J.%2C%20Han%2C%20H.%2C%20Guidry%2C%20K.%2C%20Chen%2C%20T.%2C%20Hao%2C%20Y.%2C%20Fedele%2C%20C.%2C%20Zebala%2C%20J.%20A.%2C%20Maeda%2C%20D.%20Y.%2C%20Christensen%2C%20J.%20G.%2C%20Olson%2C%20P.%2C%20Athanas%2C%20A.%2C%20Loomis%2C%20C.%20A.%2C%20Tsirigos%2C%20A.%2C%20Wong%2C%20K.-K.%2C%20%26amp%3B%20Neel%2C%20B.%20G.%20%282021%29.%20Combined%20Inhibition%20of%20SHP2%20and%20CXCR1%5C%2F2%20Promotes%20Anti-Tumor%20T%20Cell%20Response%20in%20NSCLC.%20%3Ci%3ECancer%20Discovery%3C%5C%2Fi%3E.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1158%5C%2F2159-8290.CD-21-0369%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1158%5C%2F2159-8290.CD-21-0369%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%3D3GSEF3RD%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%22Combined%20Inhibition%20of%20SHP2%20and%20CXCR1%5C%2F2%20Promotes%20Anti-Tumor%20T%20Cell%20Response%20in%20NSCLC%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kwan%20Ho%22%2C%22lastName%22%3A%22Tang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shuai%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alireza%22%2C%22lastName%22%3A%22Khodadadi-Jamayran%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jayu%22%2C%22lastName%22%3A%22Jen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Han%22%2C%22lastName%22%3A%22Han%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kayla%22%2C%22lastName%22%3A%22Guidry%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ting%22%2C%22lastName%22%3A%22Chen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yuan%22%2C%22lastName%22%3A%22Hao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Carmine%22%2C%22lastName%22%3A%22Fedele%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22John%20A.%22%2C%22lastName%22%3A%22Zebala%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Dean%20Y.%22%2C%22lastName%22%3A%22Maeda%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22James%20G.%22%2C%22lastName%22%3A%22Christensen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Peter%22%2C%22lastName%22%3A%22Olson%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Argus%22%2C%22lastName%22%3A%22Athanas%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Cynthia%20A.%22%2C%22lastName%22%3A%22Loomis%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Aristotelis%22%2C%22lastName%22%3A%22Tsirigos%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kwok-Kin%22%2C%22lastName%22%3A%22Wong%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Benjamin%20G.%22%2C%22lastName%22%3A%22Neel%22%7D%5D%2C%22abstractNote%22%3A%22SHP2%20inhibitors%20%28SHP2i%29%20alone%20and%20in%20various%20combinations%20are%20being%20tested%20in%20multiple%20tumors%20with%20over-activation%20of%20the%20RAS%5C%2FERK%20pathway.%20SHP2%20plays%20critical%20roles%20in%20normal%20cell%20signaling%3B%20hence%2C%20SHP2is%20could%20influence%20the%20tumor%20microenvironment.%20We%20found%20that%20SHP2i%20treatment%20depleted%20alveolar%20and%20M2-like%20macrophages%2C%20induced%20tumor-intrinsic%20CCL5%5C%2FCXCL10%20secretion%20and%20promoted%20B%20and%20T%20lymphocyte%20infiltration%20in%20Kras-%20and%20Egfr-mutant%20non-small%20cell%20lung%20cancer%20%28NSCLC%29.%20However%2C%20treatment%20also%20increased%20intratumor%20gMDSCs%20via%20tumor-intrinsic%2C%20NF-kB-dependent%20production%20of%20CXCR2%20ligands.%20Other%20RAS%5C%2FERK%20pathway%20inhibitors%20also%20induced%20CXCR2%20ligands%20and%20gMDSC%20influx%20in%20mice%2C%20and%20CXCR2%20ligands%20were%20induced%20in%20tumors%20from%20patients%20on%20KRASG12C-inhibitor%20trials.%20Combined%20SHP2%28SHP099%29%5C%2FCXCR1%5C%2F2%28SX682%29%20inhibition%20depleted%20a%20specific%20cluster%20of%20S100a8%5C%2F9high%20gMDSCs%2C%20generated%20Klrg1%2B%20CD8%2B%20effector%20T%20cells%20with%20a%20strong%20cytotoxic%20phenotype%20but%20expressing%20the%20checkpoint%20receptor%20NKG2A%2C%20and%20enhanced%20survival%20in%20Kras-%20and%20Egfr-mutant%20models.%20Our%20results%20argue%20for%20testing%20RAS%5C%2FERK%20pathway%5C%2FCXCR1%5C%2F2%5C%2FNKG2A%20inhibitor%20combinations%20in%20NSCLC%20patients.%22%2C%22date%22%3A%222021%5C%2F01%5C%2F01%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1158%5C%2F2159-8290.CD-21-0369%22%2C%22ISSN%22%3A%222159-8274%2C%202159-8290%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fcancerdiscovery.aacrjournals.org%5C%2Fcontent%5C%2Fearly%5C%2F2021%5C%2F07%5C%2F28%5C%2F2159-8290.CD-21-0369%22%2C%22collections%22%3A%5B%5D%2C%22dateModified%22%3A%222021-08-10T06%3A50%3A41Z%22%7D%7D%5D%7D
Tang, K. H., Li, S., Khodadadi-Jamayran, A., Jen, J., Han, H., Guidry, K., Chen, T., Hao, Y., Fedele, C., Zebala, J. A., Maeda, D. Y., Christensen, J. G., Olson, P., Athanas, A., Loomis, C. A., Tsirigos, A., Wong, K.-K., & Neel, B. G. (2021). Combined Inhibition of SHP2 and CXCR1/2 Promotes Anti-Tumor T Cell Response in NSCLC. Cancer Discovery. https://doi.org/10.1158/2159-8290.CD-21-0369 Cite
Abstract
Exit mobile version