Cancer Stem Cell News
Cell Therapy News
Dermal Cell News
Endothelial Cell News
ESC & iPSC News
Extracellular Matrix News
Hematopoiesis News
Hepatic Cell News
Human Immunology News
Immune Regulation News
Intestinal Cell News
Mammary Cell News
Mesenchymal Cell News
Muscle Cell News
Neural Cell News
Organoid News
Pancreatic Cell News
Prostate Cell News
Pulmonary Cell NewsScientists report that patients with low melanoma neoantigen burdens who responded to ICI had tumors with higher expression of pigmentation-related genes.
[Science Translational Medicine]
6445218 92EHJZ3B items 1 apa 0 default asc 1 159239 https://www.stemcellsciencenews.com/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3A%22zotpress-01d1dca2084b1c41177531263394d886%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%2292EHJZ3B%22%2C%22library%22%3A%7B%22id%22%3A6445218%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Lo%20et%20al.%22%2C%22parsedDate%22%3A%222021-02-17%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%3ELo%2C%20J.%20A.%2C%20Kawakubo%2C%20M.%2C%20Juneja%2C%20V.%20R.%2C%20Su%2C%20M.%20Y.%2C%20Erlich%2C%20T.%20H.%2C%20LaFleur%2C%20M.%20W.%2C%20Kemeny%2C%20L.%20V.%2C%20Rashid%2C%20M.%2C%20Malehmir%2C%20M.%2C%20Rabi%2C%20S.%20A.%2C%20Raghavan%2C%20R.%2C%20Allouche%2C%20J.%2C%20Kasumova%2C%20G.%2C%20Frederick%2C%20D.%20T.%2C%20Pauken%2C%20K.%20E.%2C%20Weng%2C%20Q.%20Y.%2C%20Silva%2C%20M.%20P.%20da%2C%20Xu%2C%20Y.%2C%20Sande%2C%20A.%20A.%20J.%20van%20der%2C%20%26%23x2026%3B%20Fisher%2C%20D.%20E.%20%282021%29.%20Epitope%20spreading%20toward%20wild-type%20melanocyte-lineage%20antigens%20rescues%20suboptimal%20immune%20checkpoint%20blockade%20responses.%20%3Ci%3EScience%20Translational%20Medicine%3C%5C%2Fi%3E%2C%20%3Ci%3E13%3C%5C%2Fi%3E%28581%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1126%5C%2Fscitranslmed.abd8636%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1126%5C%2Fscitranslmed.abd8636%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%3D92EHJZ3B%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%22Epitope%20spreading%20toward%20wild-type%20melanocyte-lineage%20antigens%20rescues%20suboptimal%20immune%20checkpoint%20blockade%20responses%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jennifer%20A.%22%2C%22lastName%22%3A%22Lo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Masayoshi%22%2C%22lastName%22%3A%22Kawakubo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Vikram%20R.%22%2C%22lastName%22%3A%22Juneja%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mack%20Y.%22%2C%22lastName%22%3A%22Su%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Tal%20H.%22%2C%22lastName%22%3A%22Erlich%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Martin%20W.%22%2C%22lastName%22%3A%22LaFleur%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lajos%20V.%22%2C%22lastName%22%3A%22Kemeny%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mamunur%22%2C%22lastName%22%3A%22Rashid%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mohsen%22%2C%22lastName%22%3A%22Malehmir%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%20Alireza%22%2C%22lastName%22%3A%22Rabi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Rumya%22%2C%22lastName%22%3A%22Raghavan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jennifer%22%2C%22lastName%22%3A%22Allouche%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gyulnara%22%2C%22lastName%22%3A%22Kasumova%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Dennie%20T.%22%2C%22lastName%22%3A%22Frederick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kristen%20E.%22%2C%22lastName%22%3A%22Pauken%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Qing%20Yu%22%2C%22lastName%22%3A%22Weng%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marcelo%20Pereira%20da%22%2C%22lastName%22%3A%22Silva%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yu%22%2C%22lastName%22%3A%22Xu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Anita%20A.%20J.%20van%20der%22%2C%22lastName%22%3A%22Sande%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Whitney%22%2C%22lastName%22%3A%22Silkworth%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Elisabeth%22%2C%22lastName%22%3A%22Roider%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Edward%20P.%22%2C%22lastName%22%3A%22Browne%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22David%20J.%22%2C%22lastName%22%3A%22Lieb%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Belinda%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Levi%20A.%22%2C%22lastName%22%3A%22Garraway%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Catherine%20J.%22%2C%22lastName%22%3A%22Wu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Keith%20T.%22%2C%22lastName%22%3A%22Flaherty%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Constance%20E.%22%2C%22lastName%22%3A%22Brinckerhoff%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22David%20W.%22%2C%22lastName%22%3A%22Mullins%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22David%20J.%22%2C%22lastName%22%3A%22Adams%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%22Mai%20P.%22%2C%22lastName%22%3A%22Hoang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Genevieve%20M.%22%2C%22lastName%22%3A%22Boland%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gordon%20J.%22%2C%22lastName%22%3A%22Freeman%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Arlene%20H.%22%2C%22lastName%22%3A%22Sharpe%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Dieter%22%2C%22lastName%22%3A%22Manstein%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22David%20E.%22%2C%22lastName%22%3A%22Fisher%22%7D%5D%2C%22abstractNote%22%3A%22Spreading%20the%20immune%20response%20to%20melanoma%5CnImmune%20checkpoint%20inhibitors%20%28ICIs%29%20have%20revolutionized%20treatment%20for%20patients%20with%20melanoma%2C%20although%20not%20all%20patients%20respond.%20Here%2C%20Lo%20et%20al.%20showed%20that%20patients%20with%20the%20best%20responses%20to%20ICI%20often%20develop%20immune%20responses%20to%20melanocyte-lineage%20epitopes.%20The%20authors%20then%20showed%20that%20inducing%20mutations%20in%20murine%20melanomas%20in%20combination%20with%20ICI%20resulted%20in%20T%20cell%20responses%20to%20the%20induced%20mutations%20plus%20inflammation%20that%20provoked%20epitope%20spreading%20to%20the%20targeting%20of%20healthy%20melanocyte%20antigens.%20The%20response%20to%20melanocyte%20antigens%20led%20to%20better%20long-term%20control%20of%20melanomas%20and%20rejection%20of%20secondary%20melanoma%20challenges%20a%20finding%20that%20was%20mimicked%20by%20alternatively%20inducing%20inflammation%20with%20localized%20laser%20and%20imiquimod%20treatment.%20Thus%2C%20combining%20methods%20to%20induce%20localized%20inflammation%20plus%20ICI%20may%20represent%20a%20therapeutic%20option%20for%20patients%20with%20suboptimal%20responses%20to%20ICI%20alone.%5CnAlthough%20immune%20checkpoint%20inhibitors%20%28ICIs%29%2C%20such%20as%20anti%5Cu2013programmed%20cell%20death%20protein%5Cu20131%20%28PD-1%29%2C%20can%20deliver%20durable%20antitumor%20effects%2C%20most%20patients%20with%20cancer%20fail%20to%20respond.%20Recent%20studies%20suggest%20that%20ICI%20efficacy%20correlates%20with%20a%20higher%20load%20of%20tumor-specific%20neoantigens%20and%20development%20of%20vitiligo%20in%20patients%20with%20melanoma.%20Here%2C%20we%20report%20that%20patients%20with%20low%20melanoma%20neoantigen%20burdens%20who%20responded%20to%20ICI%20had%20tumors%20with%20higher%20expression%20of%20pigmentation-related%20genes.%20Moreover%2C%20expansion%20of%20peripheral%20blood%20CD8%2B%20T%20cell%20populations%20specific%20for%20melanocyte%20antigens%20was%20observed%20only%20in%20patients%20who%20responded%20to%20anti%5Cu2013PD-1%20therapy%2C%20suggesting%20that%20ICI%20can%20promote%20breakdown%20of%20tolerance%20toward%20tumor-lineage%20self-antigens.%20In%20a%20mouse%20model%20of%20poorly%20immunogenic%20melanomas%2C%20spreading%20of%20epitope%20recognition%20toward%20wild-type%20melanocyte%20antigens%20was%20associated%20with%20markedly%20improved%20anti%5Cu2013PD-1%20efficacy%20in%20two%20independent%20approaches%3A%20introduction%20of%20neoantigens%20by%20ultraviolet%20%28UV%29%20B%20radiation%20mutagenesis%20or%20the%20therapeutic%20combination%20of%20ablative%20fractional%20photothermolysis%20plus%20imiquimod.%20Complete%20responses%20against%20UV%20mutation-bearing%20tumors%20after%20anti%5Cu2013PD-1%20resulted%20in%20protection%20from%20subsequent%20engraftment%20of%20melanomas%20lacking%20any%20shared%20neoantigens%2C%20as%20well%20as%20pancreatic%20adenocarcinomas%20forcibly%20overexpressing%20melanocyte-lineage%20antigens.%20Our%20data%20demonstrate%20that%20somatic%20mutations%20are%20sufficient%20to%20provoke%20strong%20antitumor%20responses%20after%20checkpoint%20blockade%2C%20but%20long-term%20responses%20are%20not%20restricted%20to%20these%20putative%20neoantigens.%20Epitope%20spreading%20toward%20T%20cell%20recognition%20of%20wild-type%20tumor-lineage%20self-antigens%20represents%20a%20common%20pathway%20for%20successful%20response%20to%20ICI%2C%20which%20can%20be%20evoked%20in%20neoantigen-deficient%20tumors%20by%20combination%20therapy%20with%20ablative%20fractional%20photothermolysis%20and%20imiquimod.%5CnNeoantigens%20sensitize%20melanomas%20to%20checkpoint%20blockade%20and%20trigger%20epitope%20spreading%20to%20self-antigens%2C%20a%20process%20mimicked%20by%20combination%20immunotherapy.%5CnNeoantigens%20sensitize%20melanomas%20to%20checkpoint%20blockade%20and%20trigger%20epitope%20spreading%20to%20self-antigens%2C%20a%20process%20mimicked%20by%20combination%20immunotherapy.%22%2C%22date%22%3A%222021%5C%2F02%5C%2F17%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1126%5C%2Fscitranslmed.abd8636%22%2C%22ISSN%22%3A%221946-6234%2C%201946-6242%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fstm.sciencemag.org%5C%2Fcontent%5C%2F13%5C%2F581%5C%2Feabd8636%22%2C%22collections%22%3A%5B%5D%2C%22dateModified%22%3A%222021-02-18T23%3A12%3A02Z%22%7D%7D%5D%7D
Lo, J. A., Kawakubo, M., Juneja, V. R., Su, M. Y., Erlich, T. H., LaFleur, M. W., Kemeny, L. V., Rashid, M., Malehmir, M., Rabi, S. A., Raghavan, R., Allouche, J., Kasumova, G., Frederick, D. T., Pauken, K. E., Weng, Q. Y., Silva, M. P. da, Xu, Y., Sande, A. A. J. van der, … Fisher, D. E. (2021). Epitope spreading toward wild-type melanocyte-lineage antigens rescues suboptimal immune checkpoint blockade responses. Science Translational Medicine, 13(581). https://doi.org/10.1126/scitranslmed.abd8636 Cite
