Page 144 - Haematologica Vol. 110 - January 2025

ARTICLE - Immune microenvironment in nodal PTCL
P. Stephan et al.
Differential expression of actionable receptors on immune cell subsets
We thus explored whether our strategy may unveil action- able co-stimulatory molecules, i.e., surface checkpoints with specific expression patterns in pro-tumoral subsets (Treg cells and Tconv cells containing tumor cells) versus anti-tumoral populations (CD8+ and NK cells). We first analyzed inhibitory checkpoints. As previously described,18 PD-1 was broadly expressed (an average of 40-60% posi- tive cells) across subsets (NK cells being negative for this receptor, as shown in other contexts20) (Figure 4), similarly to TIM-3 (9-57%) and TIGIT (30-70%). Conversely, few cells expressed LAG-3, and CTLA-4 was mostly found on Treg and Tconv cells (18-84% positive cells), while its expres- sion was quite low on CD8+ T cells and NK cells; this was particularly true for AITL samples. In addition, NKG2A was expressed by approximately 50% of NK cells regardless of
the pathology, and was undetected on T cells. Concerning ‘activation’ checkpoints, ICOS and OX-40 followed a pattern similar to CTLA-4, whereas 4-1BB and TNFR2 displayed low expression, the latter being preferentially expressed by Treg cells. Thus, while checkpoint receptors were gen- erally broadly expressed in PTCL, some of these targetable proteins (CTLA-4, ICOS, OX-40) showed specific expression patterns with high expression in Tconv (including tumor cells) and Treg cells, and low expression in anti-tumor effectors, indicating that they may be considered thera- peutic targets.
Increased CD39 expression in peripheral T-cell lymphoma is associated with poor prognosis
In addition to these checkpoints, belonging to the CD28 and tumor necrosis factor receptor superfamilies, we also investigated the expression levels of the ectonucleoti-
Figure 4. Differential expression pattern of checkpoint receptors on immune subsets in peripheral T-cell lymphoma. Proportion of checkpoint-expressing cells in different cell subsets following manual gating is shown as Mean + Standard Error of Mean. Two- way ANOVA tests were used. AITL: angioimmunoblastic T-cell lymphoma; PTCL, NOS: peripheral T-cell lymphoma, not otherwise specified; NK: natural killer cells. *P<0.05, *P<0.005, ***P<0.001, ****P<0.0001. Non-significant values are not displayed.
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