Ultra high content analyses of circulating and tumor associated hybrid cells reveal phenotypic heterogeneity

• Published in: Scientific reports Vol. 14; no. 1; pp. 7350 - 11
• Main Authors: Whalen, Riley M., Anderson, Ashley N., Jones, Jocelyn A., Sims, Zachary, Chang, Young Hwan, Nederlof, Michel A., Wong, Melissa H., Gibbs, Summer L.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28-03-2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67; 631/80; Antibodies; Biomarkers; Biomarkers, Tumor; Cancer; Cancer biomarker; Cancer progression; Circulating hybrid cell; Colorectal cancer; Cyclic immunofluorescence; Heterogeneity; Humanities and Social Sciences; Humans; Hybrid Cells - pathology; Hybrids; Immunofluorescence; multidisciplinary; Neoplastic Cells, Circulating - pathology; Oligonucleotide-conjugated antibody; Oligonucleotides; Peripheral blood; Phenotype; Phenotypes; Science; Science (multidisciplinary); Subpopulations; Tumor cells; Tumors; Cancer biomarker; Pancreatic cancer; Colorectal cancer; Cancer progression; Circulating hybrid cell; Cyclic immunofluorescence; Oligonucleotide-conjugated antibody
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-57381-8

Persistently high, worldwide mortality from cancer highlights the unresolved challenges of disease surveillance and detection that impact survival. Development of a non-invasive, blood-based biomarker would transform survival from cancer. We demonstrate the functionality of ultra-high content analyses of a newly identified population of tumor cells that are hybrids between neoplastic and immune cells in patient matched tumor and peripheral blood specimens. Using oligonucleotide conjugated antibodies (Ab-oligo) permitting cyclic immunofluorescence (cyCIF), we present analyses of phenotypes among tumor and peripheral blood hybrid cells. Interestingly, the majority of circulating hybrid cell (CHC) subpopulations were not identified in tumor-associated hybrids. These results highlight the efficacy of ultra-high content phenotypic analyses using Ab-oligo based cyCIF applied to both tumor and peripheral blood specimens. The combination of a multiplex phenotypic profiling platform that is gentle enough to analyze blood to detect and evaluate disseminated tumor cells represents a novel approach to exploring novel tumor biology and potential utility for developing the population as a blood-based biomarker in cancer.