Details

Autor(en) / Beteiligte

• Penter, Livius
• Zhang, Yi
• Savell, Alexandra
• Huang, Teddy
• Cieri, Nicoletta
• Thrash, Emily M.
• Kim-Schulze, Seunghee
• Jhaveri, Aashna
• Fu, Jingxin
• Ranasinghe, Srinika
• Li, Shuqiang
• Zhang, Wandi
• Hathaway, Emma S.
• Nazzaro, Matthew
• Kim, Haesook T.
• Chen, Helen
• Thurin, Magdalena
• Rodig, Scott J.
• Severgnini, Mariano
• Cibulskis, Carrie
• Gabriel, Stacey
• Livak, Kenneth J.
• Cutler, Corey
• Antin, Joseph H.
• Nikiforow, Sarah
• Koreth, John
• Ho, Vincent T.
• Armand, Philippe
• Ritz, Jerome
• Streicher, Howard
• Neuberg, Donna
• Hodi, F. Stephen
• Gnjatic, Sacha
• Soiffer, Robert J.
• Liu, X. Shirley
• Davids, Matthew S.
• Bachireddy, Pavan
• Wu, Catherine J.

Titel

Molecular and cellular features of CTLA-4 blockade for relapsed myeloid malignancies after transplantation

Ist Teil von

• Blood, 2021-06, Vol.137 (23), p.3212-3217

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• Relapsed myeloid disease after allogeneic stem cell transplantation (HSCT) remains largely incurable. We previously demonstrated the potent activity of immune checkpoint blockade in this clinical setting with ipilimumab or nivolumab. To define the molecular and cellular pathways by which CTLA-4 blockade with ipilimumab can reinvigorate an effective graft-versus-leukemia (GVL) response, we integrated transcriptomic analysis of leukemic biopsies with immunophenotypic profiling of matched peripheral blood samples collected from patients treated with ipilimumab following HSCT on the Experimental Therapeutics Clinical Trials Network 9204 trial. Response to ipilimumab was associated with transcriptomic evidence of increased local CD8+ T-cell infiltration and activation. Systemically, ipilimumab decreased naïve and increased memory T-cell populations and increased expression of markers of T-cell activation and costimulation such as PD-1, HLA-DR, and ICOS, irrespective of response. However, responding patients were characterized by higher turnover of T-cell receptor sequences in peripheral blood and showed increased expression of proinflammatory chemokines in plasma that was further amplified by ipilimumab. Altogether, these data highlight the compositional T-cell shifts and inflammatory pathways induced by ipilimumab both locally and systemically that associate with successful GVL outcomes. This trial was registered at www.clinicaltrials.gov as #NCT01822509. •Increased T-cell infiltration, activation, and peripheral chemokine expression mark ipilimumab response to relapsed leukemia after HSCT.•Similar to the nontransplant setting, ipilimumab alters peripheral memory T-cell populations and leads to global T-cell activation. [Display omitted]