Affordable Access

deepdyve-link
Publisher Website

Integrated multiomic approach for identification of novel immunotherapeutic targets in AML

Authors
  • Köhnke, Thomas
  • Liu, Xilong
  • Haubner, Sascha
  • Bücklein, Veit
  • Hänel, Gerulf
  • Krupka, Christina
  • Solis-Mezarino, Victor
  • Herzog, Franz
  • Subklewe, Marion
Type
Published Article
Journal
Biomarker Research
Publisher
BioMed Central
Publication Date
Jun 10, 2022
Volume
10
Identifiers
DOI: 10.1186/s40364-022-00390-4
PMID: 35681175
PMCID: PMC9185890
Source
PubMed Central
Keywords
Disciplines
  • Research
License
Unknown

Abstract

Background Immunotherapy of acute myeloid leukemia has experienced considerable advances, however novel target antigens continue to be sought after. To this end, unbiased approaches for surface protein detection are limited and integration with other data types, such as gene expression and somatic mutational burden, are poorly utilized. The Cell Surface Capture technology provides an unbiased, discovery-driven approach to map the surface proteins on cells of interest. Yet, direct utilization of primary patient samples has been limited by the considerable number of viable cells needed. Methods Here, we optimized the Cell Surface Capture protocol to enable direct interrogation of primary patient samples and applied our optimized protocol to a set of samples from patients with acute myeloid leukemia (AML) to generate the AML surfaceome. We then further curated this AML surfaceome to exclude antigens expressed on healthy tissues and integrated mutational burden data from hematologic cancers to further enrich for targets which are likely to be essential to leukemia biology. Finally, we validated our findings in a separate cohort of AML patient samples. Results Our protocol modifications allowed us to double the yield in identified proteins and increased the specificity from 54 to 80.4% compared to previous approaches. Using primary AML patient samples, we were able to identify a total of 621 surface proteins comprising the AML surfaceome. We integrated this data with gene expression and mutational burden data to curate a set of robust putative target antigens. Seventy-six proteins were selected as potential candidates for further investigation of which we validated the most promising novel candidate markers, and identified CD148, ITGA4 and Integrin beta-7 as promising targets in AML. Integrin beta-7 showed the most promising combination of expression in patient AML samples, and low or absent expression on healthy hematopoietic tissue. Conclusion Taken together, we demonstrate the feasibility of a highly optimized surfaceome detection method to interrogate the entire AML surfaceome directly from primary patient samples and integrate this data with gene expression and mutational burden data to achieve a robust, multiomic target identification platform. This approach has the potential to accelerate the unbiased target identification for immunotherapy of AML. Supplementary Information The online version contains supplementary material available at 10.1186/s40364-022-00390-4.

Report this publication

Statistics

Seen <100 times