Page 290 - Haematologica March 2020

M. Ando et al.
marrow from each mouse were histopathologically exam- ined. All were tumor free in gross and microscopic analy- sis (Figure 5A, upper row of panels).
After only three rejT injections ENKL tumors were entirely extirpated. By contrast, tissues from a mouse injected with original CTL that died 58 days after the first injection were densely infiltrated by ENKL cells: original
LMP2-CTL could not eradicate ENKL cells in vivo long- term. To determine whether injected rejT or original CTL persisted long-term, spleen sections were evaluated immunohistochemically. Spleens of euthanized mice that had been treated with rejT, with or without anti-PD-1 Ab, were well-populated by human CD3+ T cells. The spleen of the mouse treated with original CTL and dead at 58
A
B
Figure 5. LMP2-rejT persisted in the spleen of long-surviving extranodal NK/T- cell lymphoma, nasal type-bearing mice. (A) Representative HE-stained sections of the spleens of ENKL-bearing mice treated with LMP2-rejT (upper left, center) and tumor mass of ENKL-bearing mice treated with original LMP2-CTL (upper right). Immunohistochemical study shows human CD3+ T-cell infiltration of the spleen in ENKL-bearing mice treated with LMP2-rejT (lower left, center) and of tumor mass in ENKL-bearing mice treated with original CTL (lower right). Spleen sections from untreated mice without ENKL were used as negative control. The scale bar repre- sents 20 mm. (B) Flow cytometric analysis of tetramer+CD3+ LMP2-rejT population from peripheral blood. Central memory phenotype (CD45RA–, CD62L+, CD27+, CD95+) EBV-rejT are maintained in peripheral blood. LMP: latent membrane protein; rejT: rejuvenated cytotoxic T lymphocyte; ENKL: extranodal NK/T-cell lymphoma, nasal type; HE: hematoxylin and eosin; CTL: cytotoxic T lymphocyte; PD-1: programmed cell death 1; Ab: antibody; EBV: Epstein-Barr virus.
804
haematologica | 2020; 105(3)