{"id":7861,"date":"2017-01-17T00:00:00","date_gmt":"2017-01-16T23:00:00","guid":{"rendered":"https:\/\/idibell.cat\/blog\/2017\/01\/17\/la-inactivacio-del-gen-b2m-es-recurrent-en-el-cancer-de-pulmo-i-pot-condicionar-la-resposta-a-immunoterapia\/"},"modified":"2020-05-13T19:46:58","modified_gmt":"2020-05-13T17:46:58","slug":"la-inactivacio-del-gen-b2m-es-recurrent-en-el-cancer-de-pulmo-i-pot-condicionar-la-resposta-a-immunoterapia","status":"publish","type":"post","link":"https:\/\/idibell.cat\/2017\/01\/la-inactivacio-del-gen-b2m-es-recurrent-en-el-cancer-de-pulmo-i-pot-condicionar-la-resposta-a-immunoterapia\/","title":{"rendered":"La inactivaci\u00f3 del gen B2M \u00e9s recurrent en el c\u00e0ncer de pulm\u00f3 i pot condicionar la resposta a immunoter\u00e0pia"},"content":{"rendered":"<p>Investigadors del grup de recerca en Gens i C\u00e0ncer de l\u2019Institut d\u2019Investigaci\u00f3 Biom\u00e8dica de Bellvitge (IDIBELL) han identificat mutacions inactivadores en una s\u00e8rie de gens que codifiquen per prote\u00efnes del complexe de histocompatibilitat HLA-I, involucrades en la resposta immunol\u00f2gica i que poden condicionar la resposta dels pacients de c\u00e0ncer de pulm\u00f3 als nous tractaments amb immunoter\u00e0pia. L\u2019estudi, fruit de la col\u00b7laboraci\u00f3 amb diversos centres de recerca nacionals i internacionals, ha estat publicat a la revista <em>Clinical Cancer Research<\/em>. <\/p>\n<p> \u201cInicialment vam fer un cribatge gen\u00e8tic de tumors de c\u00e0ncer de pulm\u00f3 emprant models de xenografts, \u00e9s a dir tumors humans que creixen en ratolins, per tal d\u2019obtenir tumors amb poca c\u00e0rrega de c\u00e8l\u00b7lules normals humanes\u201d, explica la doctora Montse Sanchez-Cespedes, darrera autora del treball. La seq\u00fcenciaci\u00f3 dels tumors va permetre identificar diversos gens mutats, incloent oncogens i gens supresors tumorals coneguts, <\/p>\n<p>i d\u2019altres no descrits pr\u00e8viament. \u201cEntre aquests darrers, ens va cridar l\u2019atenci\u00f3 el gen <em>B2M<\/em> per la seva implicaci\u00f3 en el funcionament del sistema immunitari, objectiu de noves ter\u00e0pies desenvolupades per aquest tipus de c\u00e0ncers\u201d. <\/p>\n<p> En una etapa posterior es va validar la observaci\u00f3, utilitzant un ampli panell de tumors de pulm\u00f3 que va permetre determinar que la freq\u00fc\u00e8ncia de mutacions de <em>B2M<\/em> en c\u00e0ncer de pulm\u00f3 es d\u2019un 6-8%. Paral\u00b7lelament, els investigadors van demostrar que la reintroducci\u00f3 <em>de novo<\/em> d\u2019aquest gen en l\u00ednies cel\u00b7lulars que eren deficients en B2M restableix el funcionament del complexe HLA-I. <\/p>\n<p> Els nous tractaments amb immunoter\u00e0pia tenen per objectiu bloquejar l\u2019activitat de certes prote\u00efnes que inhibeixen el sistema immunitari. En c\u00e0ncer de pulm\u00f3, aquesta opci\u00f3 terap\u00e8utica ha donat resultats esperan\u00e7adors en aproximadament un vint per cent dels pacients. No obstant, el tractament nom\u00e9s pot ser efectiu si el complexe HLA-I de la c\u00e8l.lula tumoral \u00e9s funcional. <\/p>\n<p> Gr\u00e0cies a una col\u00b7laboraci\u00f3 amb el Vall d\u2019Hebron Institut d\u2019Oncologia (VHIO), l\u2019equip de l\u2019IDIBELL va poder treballar amb mostres de 14 pacients sotmesos a immunoter\u00e0pia per determinar els nivells de B2M i d\u2019altres prote\u00efnes o mol\u00e8cules relacionades amb el funcionament del complexe HLA-I. \u201cMalgrat el nombre de mostres disponibles \u00e9s limitat, vam poder observar una tend\u00e8ncia clara; en aquells pacients amb tumors que expressaven elevats nivells d\u2019aquestes prote\u00efnes la resposta a la ter\u00e0pia era superior\u201d, explica la investigadora.<\/p>\n<p> \u201cEn un futur proper, si disposem de suficients mostres, ens agradaria confirmar la correlaci\u00f3 entre l\u2019expressi\u00f3 de B2M i la resposta al tractament observada en aquest estudi\u201d, apunta la Dra. Sanchez-Cespedes. \u201cParal\u00b7lelament, intentarem buscar nous perfils gen\u00e8tics o components moleculars que puguin servir per determinar la resposta dels pacients a immunoter\u00e0pia a banda dels nivells de B2M i PD-L1 (una de les dianes d\u2019aquests tractaments), i caracteritzar d\u2019altres gens relacionats amb aquests processos immunitaris\u201d.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Investigadors del grup de recerca en Gens i C\u00e0ncer de l\u2019Institut d\u2019Investigaci\u00f3 Biom\u00e8dica de Bellvitge (IDIBELL) han identificat mutacions inactivadores en una s\u00e8rie de gens que codifiquen per prote\u00efnes del complexe de histocompatibilitat HLA-I, involucrades en la resposta immunol\u00f2gica i que poden condicionar la resposta dels pacients de c\u00e0ncer de pulm\u00f3 als nous tractaments amb 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