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

被引：5

作者：

Causer, Andrew ^{[1
]}

Tan, Xiao ^{[2
]}

Lu, Xuehan ^{[2
]}

Moseley, Philip ^{[2
]}

Teoh, Siok M. ^{[1
]}

Molotkov, Natalie ^{[2
]}

McGrath, Margaret ^{[3
]}

Kim, Taehyun ^{[4
]}

Simpson, Peter T. ^{[5
]}

Perry, Christopher ^{[6
,7
]}

Frazer, Ian H. ^{[2
]}

Panizza, Benedict ^{[6
,7
]}

Ladwa, Rahul ^{[3
,6
]}

Nguyen, Quan ^{[1
]}

Gonzalez-Cruz, Jazmina L. ^{[2
]}

机构：

[1] Univ Queensland, Inst Mol Biol, Brisbane, Qld, Australia

[2] Univ Queensland, Frazer Inst, Brisbane, Qld, Australia

[3] Princess Alexandra Hosp, Dept Med Oncol, Brisbane, Qld, Australia

[4] Royal Brisbane & Womens Hosp, Pathol Queensland, Brisbane, Qld, Australia

[5] Univ Queensland, Fac Med, UQ Ctr Clin Res, Brisbane, Qld, Australia

[6] Univ Queensland, Fac Med, Brisbane, Qld, Australia

[7] Princess Alexandra Hosp, Dept Otolaryngol Head & Neck Surg, Brisbane, Qld, Australia

来源：

NPJ PRECISION ONCOLOGY | 2023年 / 7卷 / 01期

关键词：

SQUAMOUS-CELL CARCINOMA; CANCER; EXPRESSION; RESPONSES; RECURRENT; PHASE; RNA;

D O I：

10.1038/s41698-023-00444-2

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：13