PMID- 36595660
OWN - NLM
STAT- MEDLINE
DCOM- 20230303
LR  - 20230316
IS  - 1538-8514 (Electronic)
IS  - 1535-7163 (Print)
IS  - 1535-7163 (Linking)
VI  - 22
IP  - 3
DP  - 2023 Mar 2
TI  - Exploration of Tumor Biopsy Gene Signatures to Understand the Role of the Tumor 
      Microenvironment in Outcomes to Lisocabtagene Maraleucel.
PG  - 406-418
LID - 10.1158/1535-7163.MCT-21-0506 [doi]
AB  - In the TRANSCEND NHL 001 study, 53% of patients with relapsed/refractory large 
      B-cell lymphoma (LBCL) treated with lisocabtagene maraleucel (liso-cel) achieved 
      a complete response (CR). To determine characteristics of patients who did and 
      did not achieve a CR, we examined the tumor biology and microenvironment from 
      lymph node tumor biopsies. LBCL biopsies from liso-cel-treated patients were 
      taken pretreatment and  approximately 11 days posttreatment for RNA sequencing (RNA-seq) and 
      multiplex immunofluorescence (mIF). We analyzed gene expression data from 
      pretreatment biopsies (N = 78) to identify gene sets enriched in patients who 
      achieved a CR to those with progressive disease. Pretreatment biopsies from 
      month-3 CR patients displayed higher expression levels of T-cell and 
      stroma-associated genes, and lower expression of cell-cycle genes. To interpret 
      whether LBCL samples were "follicular lymphoma (FL)-like," we constructed an 
      independent gene expression signature and found that patients with a higher 
      "FL-like" gene expression score had longer progression-free survival (PFS). Cell 
      of origin was not associated with response or PFS, but double-hit gene expression 
      was associated with shorter PFS. The day 11 posttreatment samples (RNA-seq, N = 
      73; mIF, N = 53) had higher levels of chimeric antigen receptor (CAR) T-cell 
      densities and CAR gene expression, general immune infiltration, and immune 
      activation in patients with CR. Further, the majority of T cells in the day 11 
      samples were endogenous. Gene expression signatures in liso-cel-treated patients 
      with LBCL can inform the development of combination therapies and next-generation 
      CAR T-cell therapies.
CI  - (c)2023 The Authors; Published by the American Association for Cancer Research.
FAU - Olson, N Eric
AU  - Olson NE
AUID- ORCID: 0000-0003-4587-269X
AD  - Bristol Myers Squibb, Seattle, Washington.
FAU - Ragan, Seamus P
AU  - Ragan SP
AUID- ORCID: 0000-0002-0836-1236
AD  - Bristol Myers Squibb, Seattle, Washington.
FAU - Reiss, David J
AU  - Reiss DJ
AUID- ORCID: 0000-0001-5392-3034
AD  - Bristol Myers Squibb, Seattle, Washington.
FAU - Thorpe, Jerill
AU  - Thorpe J
AUID- ORCID: 0000-0001-8772-5028
AD  - Bristol Myers Squibb, Seattle, Washington.
FAU - Kim, Yeonhee
AU  - Kim Y
AUID- ORCID: 0000-0002-3209-916X
AD  - Bristol Myers Squibb, Seattle, Washington.
FAU - Abramson, Jeremy S
AU  - Abramson JS
AUID- ORCID: 0000-0001-8467-9257
AD  - Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
AD  - Harvard Medical School, Boston, Massachusetts.
FAU - McCoy, Candice
AU  - McCoy C
AUID- ORCID: 0000-0003-1073-2822
AD  - Bristol Myers Squibb, Seattle, Washington.
FAU - Newhall, Kathryn J
AU  - Newhall KJ
AUID- ORCID: 0000-0002-6441-9316
AD  - Bristol Myers Squibb, Seattle, Washington.
FAU - Fox, Brian A
AU  - Fox BA
AUID- ORCID: 0000-0001-6620-3853
AD  - Bristol Myers Squibb, Seattle, Washington.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cancer Ther
JT  - Molecular cancer therapeutics
JID - 101132535
RN  - 0 (Receptors, Chimeric Antigen)
RN  - 0 (Antigens, CD19)
SB  - IM
MH  - Humans
MH  - Tumor Microenvironment
MH  - Biopsy
MH  - Genes, Neoplasm
MH  - *Lymphoma, Follicular
MH  - Combined Modality Therapy
MH  - Immunotherapy, Adoptive
MH  - *Lymphoma, Large B-Cell, Diffuse
MH  - *Receptors, Chimeric Antigen
MH  - Antigens, CD19
PMC - PMC9978882
EDAT- 2023/01/04 06:00
MHDA- 2023/03/04 06:00
PMCR- 2023/03/02
CRDT- 2023/01/03 15:02
PHST- 2021/06/03 00:00 [received]
PHST- 2021/12/17 00:00 [revised]
PHST- 2022/12/21 00:00 [accepted]
PHST- 2023/01/04 06:00 [pubmed]
PHST- 2023/03/04 06:00 [medline]
PHST- 2023/01/03 15:02 [entrez]
PHST- 2023/03/02 00:00 [pmc-release]
AID - 712708 [pii]
AID - MCT-21-0506 [pii]
AID - 10.1158/1535-7163.MCT-21-0506 [doi]
PST - ppublish
SO  - Mol Cancer Ther. 2023 Mar 2;22(3):406-418. doi: 10.1158/1535-7163.MCT-21-0506.