Immunotherapeutic targeting of surfaceome heterogeneity in AML

• Published in: Cell reports (Cambridge) 2024-06, Vol.43 (6), p.114260, Article 114260
• Main Authors: Bordeleau, Marie-Eve, Audemard, Éric, Métois, Arnaud, Theret, Louis, Lisi, Véronique, Farah, Azer, Spinella, Jean-François, Chagraoui, Jalila, Moujaber, Ossama, Aubert, Léo, Khakipoor, Banafsheh, Mallinger, Laure, Boivin, Isabel, Mayotte, Nadine, Hajmirza, Azadeh, Bonneil, Éric, Béliveau, François, Pfammatter, Sybille, Feghaly, Albert, Boucher, Geneviève, Gendron, Patrick, Thibault, Pierre, Barabé, Frédéric, Lemieux, Sébastien, Richard-Carpentier, Guillaume, Hébert, Josée, Lavallée, Vincent-Philippe, Roux, Philippe P., Sauvageau, Guy
• Format: Article
• Language: English
• Subjects: acute myeloid leukemia; AML antigens; CP: Cancer; Humans; immunotherapy; Immunotherapy - methods; leukemia stem cells; Leukemia, Myeloid, Acute - immunology; Leukemia, Myeloid, Acute - pathology; Leukemia, Myeloid, Acute - therapy; Membrane Proteins - metabolism; primary human AML specimens; single-cell RNA sequencing; surfaceome; therapeutic antibodies
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.114260

Immunotherapy remains underexploited in acute myeloid leukemia (AML) compared to other hematological malignancies. Currently, gemtuzumab ozogamicin is the only therapeutic antibody approved for this disease. Here, to identify potential targets for immunotherapeutic intervention, we analyze the surface proteome of 100 genetically diverse primary human AML specimens for the identification of cell surface proteins and conduct single-cell transcriptome analyses on a subset of these specimens to assess antigen expression at the sub-population level. Through this comprehensive effort, we successfully identify numerous antigens and markers preferentially expressed by primitive AML cells. Many identified antigens are targeted by therapeutic antibodies currently under clinical evaluation for various cancer types, highlighting the potential therapeutic value of the approach. Importantly, this initiative uncovers AML heterogeneity at the surfaceome level, identifies several antigens and potential primitive cell markers characterizing AML subgroups, and positions immunotherapy as a promising approach to target AML subgroup specificities. [Display omitted] •AML surfaceome analysis reveals AML antigens expressed by primitive cell populations•AML subgroups show different antigen and primitive cell marker expression profiles•This study positions immunotherapy as a promising approach to target AML heterogeneity Bordeleau et al. analyze the AML surfaceome and identify numerous antigens and markers preferentially expressed by primitive AML cells. Many identified antigens are targeted by therapeutic antibodies currently under clinical evaluation, highlighting the potential therapeutic value of the approach. This initiative demonstrates AML heterogeneity at the surfaceome level.