T-cell miR-155 regulates the response to tumor-specific mRNA vaccines in a murine model of acute myeloid leukemia.

Authors

Benjamin Battistone, Arevik Ghazaryan, William W Tang, Zekıye Büşra Ağir, Jacob Tantalla, Jacob Thompson, Kaylyn M Bauer, Cindy Barba, Morgan Nelson, Van T B Tran, Liam O'Malley, Quynh Ngo, Colton Hernandez, Amber Thibeaux, Hüseyin Atakan Ekiz, Warren P Voth, Dinesh S Rao, Ryan M O'Connell

Published in

Journal of immunology (Baltimore, Md. : 1950). Volume 215. Issue 7. Jul 10, 2026.

Abstract

Acute myeloid leukemia (AML) is a malignant clonal expansion of myeloid progenitor cells that impedes normal hematopoiesis and culminates in bone marrow failure and death. The development of chemoresistant disease in response to first-line chemotherapies is common and indicates a need for new therapies. Tumor-specific mRNA vaccines have emerged as potent inducers of cellular immunity against solid tumors, yet their utility in targeting AML and the specific mechanisms that govern their broader activity remain poorly defined. Here, we demonstrate that microRNA-155 (miR-155) within T cells is vital for host anti-leukemia responses at baseline, and for mRNA vaccine-elicited cellular responses against AML. Loss of miR-155 in T cells in conditional knockout (TCKO) mice (miR-155 fl/fl CD4+Cre) results in deficient antitumor immunity against syngeneic ovalbumin-expressing C1498 murine AML (C1498-OVA). T cell-intrinsic miR-155 is required for terminal differentiation of short-lived effector KLRG1+ CD8+ T cells, thereby providing protective immunity induced by a tumor Ag-specific mRNA vaccine against C1498-OVA AML. Single-cell RNA sequencing reveals distinct miR-155-dependent transcriptomic regulation during the mRNA vaccine response. including changes indicative of a failure to appropriately respond to IFN-γ signaling in miR-155 TCKO CD8+ T cells. Notably, we identify a subset of genes modulated by miR-155 in CD8+ T cells specific to response to mRNA vaccination, indicating a novel and context-specific role for miR-155 in regulating the immune response to mRNA-lipid nanoparticle therapeutics. Together, these data indicate T cell-expressed miR-155 is a master regulator of intrinsic cellular immunity to AML and promotes tumor-specific mRNA vaccine responses.

PMID:
42464564
Bibliographic data and abstract were imported from PubMed on 17 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.