FIG 4.

Correlative studies of tumor tissue and of blood from patients treated with axi-cel demonstrate potential mechanisms of resistance. (A and B) Two post-treatment tumor biopsy specimens stained for cluster of differentiation (CD) 19 and programmed death ligand 1 (PD-L1) by immunohistochemistry, as well as for paired box 5 (PAX5), kinesin-like protein 1 (KIP-1), CD3, and 4′,6-diamidino-2-phenylindole (DAPI) by multiplex immunofluorescence. Biopsy specimens were obtained on day 37 (A) and on day 58 (B). (C) CyTOF analysis of expression of CD4, CD8, Ki67, and iducible T cell costimulator (ICOS) of chimeric antigen receptor (CAR) T+ and CAR T− cells from 4 responding (R) and 4 nonresponding (nR) patients. (D) CyTOF comparison of intensity of expression of Ki67 and ICOS among CAR+ (KIP+) and CAR− (KIP−) CD4 as well as CD8 cells from 4 R and 4 nR patients. (E) Differences in expression of multiple cell markers between CAR+ and CAR− T cells from blood samples taken on day 7 of axicabtagene ciloleucel therapy. (F) Differences in expression of multiple cell markers stratified by CAR positivity and CD4/8 expression from serial blood samples.