1. Spatial subsetting enables integrative modeling of oral squamous cell carcinoma multiplex imaging data.
- Author
-
Einhaus J, Gaudilliere DK, Hedou J, Feyaerts D, Ozawa MG, Sato M, Ganio EA, Tsai AS, Stelzer IA, Bruckman KC, Amar JN, Sabayev M, Bonham TA, Gillard J, Diop M, Cambriel A, Mihalic ZN, Valdez T, Liu SY, Feirrera L, Lam DK, Sunwoo JB, Schürch CM, Gaudilliere B, and Han X
- Abstract
Oral squamous cell carcinoma (OSCC), a prevalent and aggressive neoplasm, poses a significant challenge due to poor prognosis and limited prognostic biomarkers. Leveraging highly multiplexed imaging mass cytometry, we investigated the tumor immune microenvironment (TIME) in OSCC biopsies, characterizing immune cell distribution and signaling activity at the tumor-invasive front. Our spatial subsetting approach standardized cellular populations by tissue zone, improving feature reproducibility and revealing TIME patterns accompanying loss-of-differentiation. Employing a machine-learning pipeline combining reliable feature selection with multivariable modeling, we achieved accurate histological grade classification (AUC = 0.88). Three model features correlated with clinical outcomes in an independent cohort: granulocyte MAPKAPK2 signaling at the tumor front, stromal CD4
+ memory T cell size, and the distance of fibroblasts from the tumor border. This study establishes a robust modeling framework for distilling complex imaging data, uncovering sentinel characteristics of the OSCC TIME to facilitate prognostic biomarkers discovery for recurrence risk stratification and immunomodulatory therapy development., Competing Interests: C.M.S. is a scientific advisor to AstraZeneca plc, and is on the scientific advisory board of, has stock options in, and has received research funding from Enable Medicine, Inc. D.K.G., J.H., and B.G. are advisory board members at SurgeCare., (© 2023 The Author(s).)- Published
- 2023
- Full Text
- View/download PDF