Molecular and immune landscape of tumours in geriatric patients with non-small cell lung cancer, melanoma and renal cell carcinoma
Abdul Rafeh Naqash,
April K Salama,
Emil Lou,
Andrew Elliott,
Wafik S El-Deiry,
Chul Kim,
Stephen V Liu,
Anwaar Saeed,
Hirva Mamdani,
Khalil Choucair,
Dipesh Uprety,
Phillip Walker,
Himisha Beltran,
Matthew James Oberley,
Azhar Saeed,
Lujia Chen
Affiliations
Abdul Rafeh Naqash
Stephenson Cancer Center, University of Oklahoma, Oklahoma City, Oklahoma, USA
April K Salama
Aff2 grid.189509.c0000000100241216Melanoma Program, Division of Medical Oncology, Department of Internal MedicineDuke University Medical Center Box 2639 203 Research Drive, MSRB1, Room 397 27710 Durham NC USA
Emil Lou
10 Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota, USA
Andrew Elliott
9Caris Life Sciences, Phoenix, AZ, USA
Wafik S El-Deiry
Brown University, Providence, Rhode Island, USA
Chul Kim
2 Division of Hematology and Oncology, Georgetown Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, USA
Stephen V Liu
Georgetown University, Washington, Washington, USA
Anwaar Saeed
4 Division of Medical Oncology, Kansas University Cancer Center, Kansas City, Kansas, USA
Hirva Mamdani
2Barbara Ann Karmanos Cancer Institute/Wayne State University, Detroit, MI, USA
Khalil Choucair
1Wayne State University, Detroit, MI, USA
Dipesh Uprety
4Barbara Ann Karmanos Cancer Institute/Wayne State University, Detroit, MI, USA
Phillip Walker
3Caris Life Sciences, Phoenix, AZ, USA
Himisha Beltran
12Dana-Farber Cancer Institute, Boston, MA, USA
Matthew James Oberley
Caris Life Sciences, Phoenix, Arizona, USA
Azhar Saeed
Department of Pathology and Laboratory Medicine, University of Vermont, Burlington, Vermont, USA
Lujia Chen
Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Objective Cancer patients aged ≥80 years present unique characteristics affecting response to immune checkpoint inhibitors (ICIs), with unidentified molecular differences. This study aimed to explore potential biomarkers of response to ICI in patients ≥80 years.Methods and analysis We analysed tumour samples (n=24 123) from patients ≥80 (versus<80) with non-small cell lung cancer (NSCLC), melanoma (MEL), and renal cell cancer (RCC). Using gene expression deconvolution, we investigated differences in tumour microenvironment (TIME) composition. Then, using next-generation sequencing and programmed death-ligand 1 (PD-L1) assessment, we evaluated gene expression differences between age groups and across tumour types, with a focus on ageing-related processes such as DNA damage response (DDR), immune checkpoint (IC) and metabolism-related genes. In a subset of patients ≥80 (n=1013), gene clustering and differential gene expression analyses were carried out to identify potential tumour-type specific expression patterns in responders to ICI.Results Significant differences in TIME composition were seen in patients with NSCLC and MEL. In patients ≥80, tumour mutational burden was lower in patients with NSCLC, higher in MEL and RCC had fewer PD-L1+tumours. DDR, IC and metabolism-related gene enrichments were distinct in patients ≥80. In patients ≥80 treated with ICIs (n=1013), there were no significant differences in survival between gene clusters, but differential gene expression analysis identified potential tumour-type specific expression patterns in responders.Conclusion Our findings reveal tumour type-specific expression profiles, TIMEs and response signatures to ICIs in patients ≥80, supporting further biomarker investigations in this population.
