Establishment and characterization of patient-derived head and neck cancer models from surgical specimens and endoscopic biopsies

Abstract

Background Head and neck squamous cell carcinoma (HNSCC) is heterogeneous in etiology, phenotype and biology. Patient-derived xenografts (PDX) maintain morphology and molecular profiling of the original tumors and have become a standard “Avatar” model for human cancer research. However, restricted availability of tumor samples hindered the widespread use of PDX. Most PDX-projects include only surgical specimens because reliable engraftment from biopsies is missing. Therefore, sample collection is limited and excludes recurrent and metastatic, non-resectable cancer from preclinical models as well as future personalized medicine. Methods This study compares the PDX-take rate, -growth, histopathology, and molecular characteristics of endoscopic specimens with surgical specimens. HNSCC samples (n = 55) were collected ad hoc, fresh frozen and implanted into NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ mice. Results Engraftment was successful in both sample types. However, engraftment rate was lower (21 vs. 52%) and growth delayed (11.2 vs. 6.7 weeks) for endoscopic biopsies. Following engraftment, growth kinetic was similar. Comparisons of primary tumors and corresponding PDX models confirmed preservation of histomorphology (HE histology) and molecular profile (Illumina Cancer Hotspot Panel) of the patients’ tumors. Accompanying flow cytometry on primary tumor specimens revealed a heterogeneous tumor microenvironment among individual cases and identified M2-like macrophages as positive predictors for engraftment. Vice versa, a high PD-L1 expression (combined positive score on tumor/immune cells) predicted PDX rejection. Conclusion Including biopsy samples from locally advanced or metastatic lesions from patients with non-surgical treatment strategies, increases the availability of PDX for basic and translational research. This facilitates (pre-) clinical studies for individual response prediction based on immunological biomarkers.

Patient-derived xenograft models in cancer therapy: technologies and applications

“… 18 (33%) N/A Shorter disease specific survival. Strüder et al 253 Head and neck squamous cell carcinoma (N/A) 16 (29%) Engraftment rate was lower and growth delayed for endoscopic biopsies. N/A Kamili et al 254 Neuroblastoma 9 (64%) Orthotopic inoculation Poor outcome Miyamoto et al 255 Cervical cancer (Adenocarcinoma, adenosquamous carcinoma, squamous cell carcinoma) 11 (50%) Large tumor size, high serum squamous cell carcinoma antigen and carbohydrate antigen 125 levels, and advanced FIGO stages.…”

Development and Evaluation of Targeted Optical Imaging Probes for Image‐Guided Surgery in Head and Neck Cancer

“…They stated the HNSCC PDX displayed morphology and molecular alterations of the paired patients and applied in surgical specimens and endoscopic biopsies. [ 159 ] Furthermore, Jordan's group assessed metabolic visualization of cetuximab treated metabolic shift in patient‐derived HNSCC models. It is also the first exam of cetuximab‐induced metabolic changes in vivo.…”

CMTM6 and PD-L1 are independent prognostic biomarkers in head and neck squamous cell carcinoma

“…Follow-up data were obtained from the regional Cancer Registries. Patients included from 01/2018 and later were additionally included in our HNSCC biobank [21]. Selection criteria were 1) primary tumor site (oral cavity, oropharynx, hypopharynx, larynx and/ or homologous neck lymph node metastases); 2) tumor size > 1.2 cm; 3) >18 years of age.…”