Hematology reports · 2025
PD-1 Expression Promotes Immune Evasion in B-ALL.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
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Casado-García Ana, García-Aguilera Gonzalo, Pozo Julio, Oak Ninad, Barrena Susana, Ruiz-Corzo Belén, Lalchandani Jaanam, Chamorro-Vera Ana, Castillo-Robleda Ana, Soriano Beatriz, Alemán-Arteaga Silvia, Sánchez Elena G, Martínez-Cano Jorge, López-Álvarez de Neyra Andrea, Somoza-Cotillas Paula, Blanco Oscar, Riesco Susana, Prieto-Matos Pablo, García Criado Francisco Javier, García Cenador María Begoña, Cobaleda César, Vicente-Dueñas Carolina, Nichols Kim E, Orfao Alberto, Ramírez-Orellana Manuel, Sánchez-García Isidro
Аннотация
BACKGROUND/OBJECTIVES: In children developing B-cell acute lymphoblastic leukemia (B-ALL), an immune evasion event takes place where otherwise "silent" preleukemic cells undergo a malignant transformation while escaping immune control, often through unknown mechanisms.
METHODS AND RESULTS: Here, we identify the upregulation of PD-1 expression in preleukemic cells, triggered by Pax5 inactivation in mice and correlating with the time of conversion to leukemia, as a novel marker that favors leukemia evasion. This increase in PD-1 expression is apparent across diverse molecular B-ALL subtypes, both in mice and humans. PD-1 is not required for B-cell leukemogenesis, but, in the absence of PD-1, tumor cells express NK cell inhibitory receptors, highlighting the necessity for leukemic cells to evade the host's NK immune response in order to exit the bone marrow. PD-1 expression reduces natural antitumor immune responses, but it sensitizes leukemic cells to immune checkpoint blockade strategies in mice and humans. PD-1 targeting confers clinical benefits by restoring NK-mediated tumor cell killing in vitro and eliminating tumor cells in vivo in mice engrafted with B-ALL.
CONCLUSIONS: These results identify PD-1 as a new therapeutic target against leukemic progression, providing new opportunities for the treatment and possibly also the prevention of childhood B-ALL.
METHODS AND RESULTS: Here, we identify the upregulation of PD-1 expression in preleukemic cells, triggered by Pax5 inactivation in mice and correlating with the time of conversion to leukemia, as a novel marker that favors leukemia evasion. This increase in PD-1 expression is apparent across diverse molecular B-ALL subtypes, both in mice and humans. PD-1 is not required for B-cell leukemogenesis, but, in the absence of PD-1, tumor cells express NK cell inhibitory receptors, highlighting the necessity for leukemic cells to evade the host's NK immune response in order to exit the bone marrow. PD-1 expression reduces natural antitumor immune responses, but it sensitizes leukemic cells to immune checkpoint blockade strategies in mice and humans. PD-1 targeting confers clinical benefits by restoring NK-mediated tumor cell killing in vitro and eliminating tumor cells in vivo in mice engrafted with B-ALL.
CONCLUSIONS: These results identify PD-1 as a new therapeutic target against leukemic progression, providing new opportunities for the treatment and possibly also the prevention of childhood B-ALL.