Discussion
tumors, CRC
TUMORS
We have identified that proliferating (Ki67While an overall sustained immune response was observed for most trial participants, some of them demonstrated insufficient maintenance of immune cellularity despite receiving naproxen treatment (Although the original ‘Naproxen Trial’ demonstrated a dose-dependent effect between low-dose and high-dose naproxen-mediated immune activation, this study showed no dose-dependent effect, which is most likely explained by the small size or random biological variation between patients. It is also possible that naproxen-mediated immune activation encompasses a broad therapeutic window, which warrants further studies to assess dose effect on T lymphocyte activation.This study utilized image mass cytometry (IMC) to quantify relative abundance of immune cells in the colonic mucosa. This powerful technique enabled high-resolution multiplexing of metal-tagged antibodies to determine naproxen sustained T-lymphocyte cellularity within the mucosal compartment of LS patients. Unlike more traditional methods such as immunofluorescence, IMC affords quantification of 40 markers within 135 detection channels. Moreover, the use of metal-tagged antibodies reduces spectral overlap and background signaling, which are often confounding disadvantages of immunofluorescence. Another advantage to IMC over more conventional methods is the customizability of metal conjugation reagents and spatial scanning of multiple regions of interest on the same slide (While this study has further identified the overall impactful role of naproxen within the normal colonic mucosa, mechanistic studies, which remain lacking, are necessary to better understanding the molecular underpinnings at play that govern immune activation and enrichment especially given the heterogeneity between different LS patients. The exploration of those studies is warranted for further studies, though it is an important and undetermined questions in the field.In summary, this work deepens our understanding of the cellular composition within the mucosal epithelium of LS carriers upon administration of naproxen for chemoprevention. Despite a more stringent schedule of annual or bi-annual colonoscopy screenings, patients with LS still develop CRC for various reasons such as rapid interval tumors (