Monitoring TIGIT/DNAM-1 and PVR/PVRL2 Immune Checkpoint Expression Levels in Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia

Abstract

After allogeneic stem cell transplantation (alloSCT), several immune checkpoints play an important role in the antileukemic immune response in the bone marrow (BM) microenvironment. However, immune checkpoint expression levels in the BM have not been reported after alloSCT in patients with acute myeloid leukemia (AML). We investigated the clinical impact of immune checkpoint expression in BM samples after alloSCT for AML. Higher expression of T cell immunoreceptor with Ig and ITIM domains (TIGIT) was associated with a decreased incidence of acute graft-versus-host disease (P = .048) and poor overall (P = .046) and progression-free survival (P = 0.024). In addition, higher expression of TIGIT at engraftment after alloSCT was correlated with a decreased number of natural killer cells in BM (P = .019). Monitoring TIGIT expression in the BM could be useful for predicting outcome after alloSCT for AML. Our findings raise the possibility that blockade of TIGIT would improve survival.

T cell reconstitution after lymphocyte depletion features a different pattern of inhibitory receptor expression in ABO- versus HLA-incompatible kidney transplant recipients

“…Hence, TIGIT emerges as a candidate for anti‐tumoral immune therapy, which is currently being tested in clinical studies . Interestingly, high TIGIT expression has also being observed in allogenic hematopoietic stem cell transplantation, where it may mitigate the severity of graft‐ versus ‐host disease (GVHD) . In ABOi patients, TIGIT expression was negatively associated with cytokine production in CD4 + T cells, suggesting it could be a marker of hypofunctional, or exhausted, T cells, as described in other conditions .…”

NK Cell-Based Immune Checkpoint Inhibition

“…Higher TIGIT expression also had lower NK cell counts in the BM after alloSCT, suggesting that TIGIT might play a crucial role in the GVL effect and GVHD to control NK cell activity and proliferation after alloSCT. Based on these observations, it was suggested that TIGIT could be a prognostic predictor after alloSCT and that its blocking could be a potent immunotherapeutic strategy to intensify the graft-vs.leukemia effect after alloSCT in AML patients (162). Hodgkin and Reed-Sternberg (HRS) cells or Tregs are involved in the inhibition of Th1, CD8 + T cells, and NK cell activity through PD-1 (163).…”

TIGIT blockade enhances functionality of peritoneal NK cells with altered expression of DNAM-1/TIGIT/CD96 checkpoint molecules in ovarian cancer

“…32 Moreover, NK cells expressing high levels of TIGIT were associated with poor survival in AML patients. 36 These TIGIT high NK cells were found to be more susceptible to myeloid-derived suppressor cell (MDSC) inhibition compared to TIGIT low NK cells. 37 Furthermore, TIGIT could be upregulated through recombinant human (rh)IL-15 stimulation, which was associated with lower IFNγ production.…”