Targeting CCR7-PI3Kγ overcomes resistance to tyrosine kinase
inhibitors in ALK-rearranged lymphoma

J 2023

Targeting CCR7-PI3Kγ overcomes resistance to tyrosine kinase inhibitors in ALK-rearranged lymphoma

MASTINI, Cristina, Marco CAMPISI, Enrico PATRUCCO, Giulia MURA, Antonio FERREIRA et. al.

Základní údaje

Originální název

Targeting CCR7-PI3Kγ overcomes resistance to tyrosine kinase inhibitors in ALK-rearranged lymphoma

Autoři

MASTINI, Cristina, Marco CAMPISI, Enrico PATRUCCO, Giulia MURA, Antonio FERREIRA, Carlotta COSTA, Chiara AMBROGIO, Giulia GERMENA, Cinzia MARTINENGO, Silvia PEOLA, Ines MOTA, Elena VISSIO, Luca MOLINARO, Maddalena ARIGONI, Martina OLIVERO, Raffaele CALOGERO, Nina PROKOPH, Fabrizio TABBO, Brent SHOJI, Laurence BRUGIERES, Birgit GEOERGER, Suzanne Dawn TURNER (826 Velká Británie a Severní Irsko, domácí), Carlos CUESTA-MATEOS, Deborah ALIBERTI, Luca MOLOGNI, Rocco PIAZZA, Carlo GAMBACORTI-PASSERINI, Giorgio G INGHIRAMI, Valeria CHIONO, Roger D KAMM, Emilio HIRSCH, Raphael KOCH, David M WEINSTOCK, Jon C ASTER, Claudia VOENA a Roberto CHIARLE

Vydání

Science Translational Medicine, Washington, American Association for the Advancement of Science, 2023, 1946-6234

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 17.100 v roce 2022

Kód RIV

RIV/00216224:14110/23:00132237

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1126/scitranslmed.abo3826

UT WoS

001021683100002

Klíčová slova anglicky

CCR7-PI3Kγ; yrosine kinase inhibitors; ALK-rearranged lymphoma

Štítky

14110323, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 14. 11. 2023 15:08, Mgr. Tereza Miškechová

Anotace

V originále

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) show potent efficacy in several ALK-driven tumors, but the development of resistance limits their long-term clinical impact. Although resistance mechanisms have been studied extensively in ALK-driven non-small cell lung cancer, they are poorly understood in ALK-driven anaplastic large cell lymphoma (ALCL). Here, we identify a survival pathway supported by the tumor microenvironment that activates phosphatidylinositol 3-kinase ? (PI3K-?) signaling through the C-C motif chemokine receptor 7 (CCR7). We found increased PI3K signaling in patients and ALCL cell lines resistant to ALK TKIs. PI3K? expression was predictive of a lack of response to ALK TKI in patients with ALCL. Expression of CCR7, PI3K?, and PI3Kd were up-regulated during ALK or STAT3 inhibition or degradation and a constitutively active PI3K? isoform cooperated with oncogenic ALK to accelerate lymphomagenesis in mice. In a three-dimensional microfluidic chip, endothelial cells that produce the CCR7 ligands CCL19/CCL21 protected ALCL cells from apoptosis induced by crizotinib. The PI3K?/d inhibitor duvelisib potentiated crizotinib activity against ALCL lines and patient-derived xenografts. Furthermore, genetic deletion of CCR7 blocked the central nervous system dissemination and perivascular growth of ALCL in mice treated with crizotinib. Thus, blockade of PI3K? or CCR7 signaling together with ALK TKI treatment reduces primary resistance and the survival of persister lymphoma cells in ALCL.

Návaznosti

LX22NPO5102, projekt VaV

Název: Národní ústav pro výzkum rakoviny (Akronym: NÚVR)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní ústav pro výzkum rakoviny, 5.1 EXCELES

Citovat

MASTINI, Cristina, Marco CAMPISI, Enrico PATRUCCO, Giulia MURA, Antonio FERREIRA, Carlotta COSTA, Chiara AMBROGIO, Giulia GERMENA, Cinzia MARTINENGO, Silvia PEOLA, Ines MOTA, Elena VISSIO, Luca MOLINARO, Maddalena ARIGONI, Martina OLIVERO, Raffaele CALOGERO, Nina PROKOPH, Fabrizio TABBO, Brent SHOJI, Laurence BRUGIERES, Birgit GEOERGER, Suzanne Dawn TURNER, Carlos CUESTA-MATEOS, Deborah ALIBERTI, Luca MOLOGNI, Rocco PIAZZA, Carlo GAMBACORTI-PASSERINI, Giorgio G INGHIRAMI, Valeria CHIONO, Roger D KAMM, Emilio HIRSCH, Raphael KOCH, David M WEINSTOCK, Jon C ASTER, Claudia VOENA a Roberto CHIARLE. Targeting CCR7-PI3Kγ overcomes resistance to tyrosine kinase inhibitors in ALK-rearranged lymphoma. Science Translational Medicine. Washington: American Association for the Advancement of Science, 2023, roč. 15, č. 702, s. 1-17. ISSN 1946-6234. Dostupné z: https://dx.doi.org/10.1126/scitranslmed.abo3826.

@article{2339258,
   author = {Mastini, Cristina and Campisi, Marco and Patrucco, Enrico and Mura, Giulia and Ferreira, Antonio and Costa, Carlotta and Ambrogio, Chiara and Germena, Giulia and Martinengo, Cinzia and Peola, Silvia and Mota, Ines and Vissio, Elena and Molinaro, Luca and Arigoni, Maddalena and Olivero, Martina and Calogero, Raffaele and Prokoph, Nina and Tabbo, Fabrizio and Shoji, Brent and Brugieres, Laurence and Geoerger, Birgit and Turner, Suzanne Dawn and CuestaandMateos, Carlos and Aliberti, Deborah and Mologni, Luca and Piazza, Rocco and GambacortiandPasserini, Carlo and Inghirami, Giorgio G and Chiono, Valeria and Kamm, Roger D and Hirsch, Emilio and Koch, Raphael and Weinstock, David M and Aster, Jon C and Voena, Claudia and Chiarle, Roberto},
   article_location = {Washington},
   article_number = {702},
   doi = {http://dx.doi.org/10.1126/scitranslmed.abo3826},
   keywords = {CCR7-PI3Kγ; yrosine kinase inhibitors; ALK-rearranged lymphoma},
   language = {eng},
   issn = {1946-6234},
   journal = {Science Translational Medicine},
   title = {Targeting CCR7-PI3Kγ overcomes resistance to tyrosine kinase inhibitors in ALK-rearranged lymphoma},
   url = {https://www.science.org/doi/10.1126/scitranslmed.abo3826},
   volume = {15},
   year = {2023}
}

TY  - JOUR
ID  - 2339258
AU  - Mastini, Cristina - Campisi, Marco - Patrucco, Enrico - Mura, Giulia - Ferreira, Antonio - Costa, Carlotta - Ambrogio, Chiara - Germena, Giulia - Martinengo, Cinzia - Peola, Silvia - Mota, Ines - Vissio, Elena - Molinaro, Luca - Arigoni, Maddalena - Olivero, Martina - Calogero, Raffaele - Prokoph, Nina - Tabbo, Fabrizio - Shoji, Brent - Brugieres, Laurence - Geoerger, Birgit - Turner, Suzanne Dawn - Cuesta-Mateos, Carlos - Aliberti, Deborah - Mologni, Luca - Piazza, Rocco - Gambacorti-Passerini, Carlo - Inghirami, Giorgio G - Chiono, Valeria - Kamm, Roger D - Hirsch, Emilio - Koch, Raphael - Weinstock, David M - Aster, Jon C - Voena, Claudia - Chiarle, Roberto
PY  - 2023
TI  - Targeting CCR7-PI3Kγ overcomes resistance to tyrosine kinase inhibitors in ALK-rearranged lymphoma
JF  - Science Translational Medicine
VL  - 15
IS  - 702
SP  - 1-17
EP  - 1-17
PB  - American Association for the Advancement of Science
SN  - 19466234
KW  - CCR7-PI3Kγ
KW  - yrosine kinase inhibitors
KW  - ALK-rearranged lymphoma
UR  - https://www.science.org/doi/10.1126/scitranslmed.abo3826
N2  - Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) show potent efficacy in several ALK-driven tumors, but the development of resistance limits their long-term clinical impact. Although resistance mechanisms have been studied extensively in ALK-driven non-small cell lung cancer, they are poorly understood in ALK-driven anaplastic large cell lymphoma (ALCL). Here, we identify a survival pathway supported by the tumor microenvironment that activates phosphatidylinositol 3-kinase ? (PI3K-?) signaling through the C-C motif chemokine receptor 7 (CCR7). We found increased PI3K signaling in patients and ALCL cell lines resistant to ALK TKIs. PI3K? expression was predictive of a lack of response to ALK TKI in patients with ALCL. Expression of CCR7, PI3K?, and PI3Kd were up-regulated during ALK or STAT3 inhibition or degradation and a constitutively active PI3K? isoform cooperated with oncogenic ALK to accelerate lymphomagenesis in mice. In a three-dimensional microfluidic chip, endothelial cells that produce the CCR7 ligands CCL19/CCL21 protected ALCL cells from apoptosis induced by crizotinib. The PI3K?/d inhibitor duvelisib potentiated crizotinib activity against ALCL lines and patient-derived xenografts. Furthermore, genetic deletion of CCR7 blocked the central nervous system dissemination and perivascular growth of ALCL in mice treated with crizotinib. Thus, blockade of PI3K? or CCR7 signaling together with ALK TKI treatment reduces primary resistance and the survival of persister lymphoma cells in ALCL.
ER  -

MASTINI, Cristina, Marco CAMPISI, Enrico PATRUCCO, Giulia MURA, Antonio FERREIRA, Carlotta COSTA, Chiara AMBROGIO, Giulia GERMENA, Cinzia MARTINENGO, Silvia PEOLA, Ines MOTA, Elena VISSIO, Luca MOLINARO, Maddalena ARIGONI, Martina OLIVERO, Raffaele CALOGERO, Nina PROKOPH, Fabrizio TABBO, Brent SHOJI, Laurence BRUGIERES, Birgit GEOERGER, Suzanne Dawn TURNER, Carlos CUESTA-MATEOS, Deborah ALIBERTI, Luca MOLOGNI, Rocco PIAZZA, Carlo GAMBACORTI-PASSERINI, Giorgio G INGHIRAMI, Valeria CHIONO, Roger D KAMM, Emilio HIRSCH, Raphael KOCH, David M WEINSTOCK, Jon C ASTER, Claudia VOENA a Roberto CHIARLE. Targeting CCR7-PI3Kγ overcomes resistance to tyrosine kinase inhibitors in ALK-rearranged lymphoma. \textit{Science Translational Medicine}. Washington: American Association for the Advancement of Science, 2023, roč.~15, č.~702, s.~1-17. ISSN~1946-6234. Dostupné z: https://dx.doi.org/10.1126/scitranslmed.abo3826.

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