Center for Global Research Data

Analysis of gene expression profiles in melanoma tumors exhibiting differential lactate dehydrogenase biomarker levels and correlation with immunotherapy response

Lead Investigator: Jason Luke, University of Pittsburgh
Title of Proposal Research: Analysis of gene expression profiles in melanoma tumors exhibiting differential lactate dehydrogenase biomarker levels and correlation with immunotherapy response
Vivli Data Request: 7101
Funding Source: None
Potential Conflicts of Interest: Scientific Advisory Board: (no stock) 7 Hills, Spring bank (stock) Actym, Alphamab Oncology, Arch Oncology, Kanaph, Mavu, Onc.AI, Pyxis, Tempest
Consultancy with compensation: Abbvie, Alnylam, Array, Bayer, Bristol-Myers Squibb, Checkmate, Cstone, Eisai, EMD Serono, KSQ, Janssen, Inzen, Macrogenics, Merck, Mersana, Nektar, Novartis, Pfizer, Regeneron, Ribon, Rubius, Silicon, Synlogic, TRex, Werewolf, Xilio, Xencor. Research Support: (all to institution for clinical trials unless noted) AbbVie, Agios (IIT), Array (IIT), Astellas, Bristol-Myers Squibb (IIT & industry), Corvus, EMD Serono, Immatics, Incyte, Kadmon, Macrogenics, Merck, Moderna, Nektar, Numab, Replimmune, Rubius, Spring bank, Synlogic, Takeda, Trishula, Tizona, Xencor. Patents: (both provisional) Serial #15/612,657 (Cancer Immunotherapy), PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof). Riyue Bao declares patents: (all provisional) PCT/US15/612657 (Cancer Immunotherapy), PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof), PCT/US63/055227 (Methods and Compositions for Treating Autoimmune and Allergic Disorders);

Summary of the Proposed Research:

Immunotherapy has transformed the treatment of cancer patients, especially in the field of melanoma. However, most patients do not respond to immune-based therapies. Thus investigating reliable, predictive biomarkers is critically important to identify patients who will respond to immunotherapy. Lactate dehydrogenase (LDH) is a commonly used blood-based biomarker associated with tumor progression in many cancers, including melanoma. However, its correlation with immune cell infiltration, and thus response to checkpoint inhibitors, is unknown. Prior research has associated LDH levels with anaerobic metabolism, lactate production, and neovascularization via vascular endothelial growth factor (VEGF). Furthermore, VEGF is associated with immune cell inhibition. Therefore, we hypothesize that LDH levels may serve as a correlative biomarker with immune cell inhibition, and thus, resistance to checkpoint blockade. In this study, we aim to find associations between clinical LDH levels and several gene signatures, including T cell-inflamed and metabolic expression patterns, along with overall clinical course and response to checkpoint blockade.

Requested Studies:
Riaz et al (2017), Cell – clinical LDH levels
Data Contributor: Bristol Myers Squibb

Grasso et al (2020), Cancer Cell. – RNAseq and DNAseq data
Data Contributor: Bristol Myers Squibb