The EACR’s ‘Highlights in Cancer Research’ is a regular summary of the most interesting and impactful recent papers in cancer research, curated by the Board of the European Association for Cancer Research (EACR).
The list below appears in no particular order, and the summary information has been provided by the authors unless otherwise indicated.
Rovira-Clavé, X., Drainas, A., P., Jinag, S., et al. Cancer Cell. 40 (11): 1423-1439. (2022).
doi: 10.1016/j.ccell.2022.09.014.
Summary of the findings
Intratumoral heterogeneity is associated with tumor progression and lack of response to treatment in patients with cancer. Despite advances in single-cell technologies, accurately tracking phenotypes and clonal evolution in situ within tumors remains a challenge. To address this issue, we have developed epitopes for imaging using combinatorial tagging (EpicTags). This tool was coupled with multiplexed ion beam imaging (MIBI) to create EpicMIBI, a technology that enables subcellular imaging of 40 proteins and in situ tracking of barcodes within tissue microenvironments. We used EpicMIBI to examine the spatial components of cell lineages and phenotypes in xenograft models of small-cell lung cancer; these tumors typically contain neuroendocrine (NE) and non-neuroendocrine cells (non-NE). We discovered that a small population of the non-neuroendocrine cells expanded to form large clonal patches, whereas neuroendocrine cancer cells did not. In addition, regions within the tumor had unique architectures; some contained large clonally diverse cell patches, and in other regions, the clonally diverse cell patches were smaller and disseminated. Lastly, epicMIBI can track the effects of genetic manipulations in subpopulations of cancer cells within a tumor. In a tumor model containing PTEN-deficient cancer cells, we observed a non-autonomous increase of clonal patch size in PTEN wild-type cancer cells.
Future impact
EpicMIBI allows tracking of phenotypes and clonal evolution in situ and enables investigation of both cell-intrinsic and cell-extrinsic processes involved in intratumoral heterogeneity. Combined with the ability to track hundreds of genetically modified cells, future work employing this technology will allow identification of causal relations between genotypes and phenotypes in the tumor microenvironment including the cancer-cell compartment and the stromal and immune cell compartments. This technique is a valuable tool for understanding tumor evolution and response to treatment and may ultimately lead to the development of more effective, personalized cancer therapies.
Summary of the findings
