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

Sci Rep. 2024 Mar 28;14(1):7350. doi: 10.1038/s41598-024-57381-8.

Abstract

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.

Keywords: Cancer biomarker; Cancer progression; Circulating hybrid cell; Colorectal cancer; Cyclic immunofluorescence; Oligonucleotide-conjugated antibody; Pancreatic cancer.

MeSH terms

  • Antibodies
  • Biomarkers, Tumor
  • Humans
  • Hybrid Cells / pathology
  • Neoplastic Cells, Circulating* / pathology
  • Phenotype

Substances

  • Biomarkers, Tumor
  • Antibodies