Integrative genomic analysis identifies unique immune environments associated with immunotherapy response in diffuse large B cell lymphoma. uri icon

Overview

abstract

  • Most diffuse large B-cell lymphoma (DLBCL) patients treated with bispecific antibodies (BsAb) or chimeric antigen receptor (CAR) T cells fail to achieve durable treatment responses, underscoring the need for a deeper understanding of mechanisms that regulate the immune environment and response to treatment. Here, an integrative, multi-omic approach was employed to characterize DLBCL immune environments, which effectively segregated DLBCLs into four quadrants - termed DLBCL-immune quadrants (IQ) - defined by cell-of-origin and immune-related gene set expression scores. Recurrent genomic alterations were enriched in each IQ, suggesting that lymphoma cell-intrinsic alterations contribute to orchestrating unique DLBCL immune environments. In relapsed/refractory DLBCL patients, DLBCL-IQ assignment correlated significantly with clinical benefit with the CD20 x CD3 BsAb, mosunetuzumab, but not with CD19-directed CAR T cells. DLBCL-IQ provides a new framework to conceptualize the DLBCL immune landscape and uncovers the differential impact of the endogenous immune environment on outcomes to BsAb and CAR T cell treatment.

authors

  • Tumuluru, Sravya
  • Godfrey, James K
  • Cooper, Alan
  • Yu, Jovian
  • Chen, Xiufen
  • MacNabb, Brendan W
  • Venkataraman, Girish
  • Zha, Yuanyuan
  • Pelzer, Benedikt
  • Song, Joo
  • Duns, Gerben
  • Bolen, Christopher
  • Bolen, Christopher
  • Penuel, Elicia
  • Kotlov, Nikita
  • Bagaev, Aleksander
  • Bagaev, Aleksander
  • Fowler, Nathan
  • Smith, Sonali M
  • Alizadeh, Ash A
  • Steidl, Christian
  • Kline, Justin

publication date

  • April 5, 2024

Identity

PubMed Central ID

  • PMC10849512

Digital Object Identifier (DOI)

  • 10.1101/2024.01.17.576100

PubMed ID

  • 38328071