PD-1/PD-L1 immune checkpoint signaling in MPN

Current understanding

PD-1/PD-L1 immune checkpoint signaling is increasingly implicated in MPN immune evasion, with JAK-STAT-driven inflammation upregulating PD-L1 on malignant clones and exhausting effector T cells. Emerging evidence (e.g., PD-L1/CXCR3 coexpression on intermediate monocytes correlating with fibrosis and leukemic transformation) suggests checkpoint blockade may complement JAK inhibition, motivating combination trials such as fedratinib + nivolumab in JAKi-resistant myelofibrosis.

Evidence log

• 2026-07-01 — CASPALLO: Allodepleted T Cells Transduced With Inducible Caspase 9 Suicide Gene: CASPALLO iCasp9 suicide-gene T-cell platform represents a distinct post-transplant immune-reconstitution strategy that operates orthogonally to PD-1/PD-L1 checkpoint modulation, controlling alloreactivity via engineered apoptosis rather than checkpoint blockade. (novelty: 4)
• 2026-06-11 — Elotuzumab for the Treatment of JAK2-Mutated Myelofibrosis: Elotuzumab phase II in JAK2-mutated MF adds a SLAMF7-targeted ADCC/NK-activating immunotherapy as a mechanistically distinct alternative to PD-1/PD-L1 checkpoint blockade for overcoming MPN immune evasion. (novelty: 4)
• 2026-05-15 — Identification of MPN-specific Antigens and Anti-MPN TCRs in Myeloproliferative Neoplasm: Observational antigen/TCR discovery effort in MPN proposes adoptive TCR therapy as an adaptive-immunity axis complementary to PD-1/PD-L1 checkpoint blockade for overcoming MPN immune evasion. (novelty: 4)
• 2026-01-29 — Guadecitabine and Atezolizumab in Treating Patients With Advanced Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia That Is Refractory or Relapsed: Guadecitabine + atezolizumab phase I/II in R/R MDS/CMML probes whether HMA-induced derepression of endogenous retroviruses and tumor antigens sensitizes myeloid malignancies to PD-L1 blockade. (novelty: 3)
• 2026-04-03 — A Phase 1 Trial of CIML NK Cell Infusion for Myeloid Disease Relapse After Hematopoietic Cell Transplantation: A Phase 1 trial of CIML NK cell infusion + IL-2 for post-transplant myeloid relapse (AML/MDS/MPN) highlights an alternative innate-immune route to overcome immune evasion, complementary to PD-1/PD-L1 checkpoint blockade strategies. (novelty: 4)
• 2026-04-08 — Fedratinib in Combination With Nivolumab: cross-connection with jak-stat-signaling: Fedratinib + nivolumab combination posits that JAK-STAT-driven immune evasion via PD-1/PD-L1 upregulation can be co-targeted, linking JAK inhibition to checkpoint blockade in JAKi-failure MF. (novelty: 4)

Open questions

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