Deep spatial-omics analysis of Head & Neck carcinomas provides alternative therapeutic targets and rationale for treatment failure

Andrew Causer; Xiao Tan; Xuehan Lu; Philip Moseley; Siok M Teoh; Natalie Molotkov; Margaret McGrath; Taehyun Kim; Peter T Simpson; Christopher Perry; Ian H Frazer; Benedict Panizza; Rahul Ladwa; Quan Nguyen; Jazmina L Gonzalez-Cruz

doi:10.1038/s41698-023-00444-2

Deep spatial-omics analysis of Head & Neck carcinomas provides alternative therapeutic targets and rationale for treatment failure

NPJ Precis Oncol. 2023 Sep 13;7(1):89. doi: 10.1038/s41698-023-00444-2.

Authors

Andrew Causer^#¹, Xiao Tan^#², Xuehan Lu², Philip Moseley², Siok M Teoh¹, Natalie Molotkov², Margaret McGrath³, Taehyun Kim⁴, Peter T Simpson⁵, Christopher Perry^{6

7}, Ian H Frazer², Benedict Panizza^{6

7}, Rahul Ladwa^{3

6}, Quan Nguyen⁸, Jazmina L Gonzalez-Cruz⁹

Affiliations

¹ Institute of Molecular Biology, The University of Queensland, Brisbane, QLD, Australia.
² Frazer Institute, The University of Queensland, Brisbane, QLD, Australia.
³ Department of Medical Oncology, Princess Alexandra Hospital, Brisbane, QLD, Australia.
⁴ Pathology Queensland, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia.
⁵ UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
⁶ Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
⁷ Department of Otolaryngology-Head & Neck surgery, Princess Alexandra Hospital, Brisbane, QLD, Australia.
⁸ Institute of Molecular Biology, The University of Queensland, Brisbane, QLD, Australia. [email protected].
⁹ Frazer Institute, The University of Queensland, Brisbane, QLD, Australia. [email protected].

^# Contributed equally.

Abstract

Immune checkpoint inhibitor (ICI) therapy has had limited success (<30%) in treating metastatic recurrent Head and Neck Oropharyngeal Squamous Cell Carcinomas (OPSCCs). We postulate that spatial determinants in the tumor play a critical role in cancer therapy outcomes. Here, we describe the case of a male patient diagnosed with p16⁺ OPSCC and extensive lung metastatic disease who failed Nivolumab and Pembrolizumab/Lenvatinib therapies. Using advanced integrative spatial proteogenomic analysis on the patient's recurrent OPSCC tumors we demonstrate that: (i) unbiased tissue clustering based on spatial transcriptomics (ST) successfully detected tumor cells and enabled the investigation of phenotypic traits such as proliferation or drug-resistance genes in the tumor's leading-edge and core; (ii) spatial proteomic imagining used in conjunction with ST (SpiCi, Spatial Proteomics inferred Cell identification) can resolve the profiling of tumor infiltrating immune cells, (iii) ST data allows for the discovery and ranking of clinically relevant alternative medicines based on their interaction with their matching ligand-receptor. Importantly, when the spatial profiles of ICI pre- and post-failure OPSCC tumors were compared, they exhibited highly similar PD-1/PD-L1^low and VEGFA^high expression, suggesting that these new tumors were not the product of ICI resistance but rather of Lenvatinib dose reduction due to complications. Our work establishes a path for incorporating spatial-omics in clinical settings to facilitate treatment personalization.