Chemotherapy induces myeloid-driven spatially confined T cell exhaustion in ovarian cancer
Cancer Cell. 2024;42(12):2045-2063.e10. DOI 10.1016/j.ccell.2024.11.005.
How to cite
AMA
Launonen IM, Niemiec I, Hincapié-Otero M, Erkan EP, Junquera A, Afenteva D, et al. Chemotherapy induces myeloid-driven spatially confined T cell exhaustion in ovarian cancer. Cancer Cell. 2024;42(12):2045-2063.e10. doi:10.1016/j.ccell.2024.11.005APA
Launonen, I.-M., Niemiec, I., Hincapié-Otero, M., Erkan, E. P., Junquera, A., Afenteva, D., et al. (2024). Chemotherapy induces myeloid-driven spatially confined T cell exhaustion in ovarian cancer. Cancer Cell, 42(12), 2045-2063.e10. https://doi.org/10.1016/j.ccell.2024.11.005BibTeX
@article{launonen2024chemotherapy,
title = {Chemotherapy induces myeloid-driven spatially confined T cell exhaustion in ovarian cancer},
author = {Launonen, Inga-Maria and Niemiec, Iga and Hincapié-Otero, María and Erkan, Erdogan Pekcan and Junquera, Ada and Afenteva, Daria and others},
journal = {Cancer Cell},
volume = {42},
number = {12},
pages = {2045--2063.e10},
year = {2024},
doi = {10.1016/j.ccell.2024.11.005}
}High-grade serous ovarian cancer is usually treated with chemotherapy, but how that treatment reshapes the immune cells around the tumor has stayed unclear. Researchers profiled 117 tumor samples taken before and after chemotherapy, combining genomics, single-cell sequencing, spatial transcriptomics, and high-plex imaging of intact tissue. After chemotherapy, myeloid cells organized into interconnected networks the authors call Myelonets, and CD8+ T cells caught inside those networks became exhausted — locally, not everywhere. The same myeloid cells signaled to T cells through a receptor pair, NECTIN2-TIGIT, and tumors with strong NECTIN2-TIGIT signaling responded to immune checkpoint blockade in a patient-derived test. The work points to myeloid-driven, spatially confined T cell exhaustion as a treatable feature of chemotherapy-treated ovarian cancer.
Key findings
- Whole-slide high-plex imaging mapped myeloid networks — “Myelonets” — that spatially confine CD8+ T cell exhaustion after chemotherapy. Across 22 tumor samples, t-CyCIF imaging on the CyteFinder resolved 6,402,172 single cells in intact tissue, and CD8+ T cells engaging myeloid cells inside Myelonets carried higher exhaustion-marker (TIM3) expression than those outside them.
- Macrophage M1/M2 polarization at the tumor-stroma interface tracked with CD8+ T cell exhaustion and exclusion, and correlated with poor chemotherapy response. A neighborhood analysis of the imaged tissue resolved 18 recurrent cellular neighborhoods, and the tumor-stroma interface showed the highest diversity of cell types and marker expression.
- Chemotherapy induced NECTIN2-TIGIT signaling between myeloid and CD8+ T cells, and tumors with high NECTIN2-TIGIT signaling responded to immune checkpoint blockade in a patient-derived platform. This molecular and functional evidence came from single-cell and spatial transcriptomics and ex vivo assays across the 117-sample cohort, not the imaging arm.
CyteFinder in the methods
“The samples were stained consecutively with the validated antibodies (Table S5 related to STAR Methods, experiment 1) followed by scanning with the RareCyte CyteFinder scanner with the t- CyCIF protocol.”
— Launonen et al., Cancer Cell (2024), STAR Methods, “Highplex t-CyCIF imaging and image processing”
Disclosure: RareCyte is named in the competing-interests statement of the publication cited above.
Why it matters for CyteFinder users
If you are weighing the CyteFinder for a tissue study, look at the specific job it did here. This was a multi-omic study: genomics, single-cell sequencing, and spatial transcriptomics each read the molecular state of the tumor, but none of them shows where a given cell sits or which cells it touches. That is the question the imaging answered. The authors ran high-plex cyclic immunofluorescence (t-CyCIF) on intact tumor sections, staining lineage and functional markers across successive rounds, then scanned each cycle on the CyteFinder and registered them into one whole-slide image. From those images — 6,402,172 single cells across 22 samples — they mapped the Myelonets, measured M1/M2 macrophage polarization at the tumor-stroma interface, and showed that CD8+ T cell exhaustion was confined to cells caught inside the myeloid networks. The molecular signaling and the checkpoint-blockade response came from the sequencing and functional arms, not the imaging. For your own work the point is concrete: when a finding turns on which cells carry a marker and who their neighbors are in tissue you cannot dissociate, whole-slide cyclic imaging is the measurement that locates it.
