Tumor-derived GDF-15 suppresses immunotherapy response NatureComms Uniklinikum_Wue DKFZ tumor cancer oncology immunotherapy immunology disease
By Pooja Toshniwal PahariaJul 26 2023Reviewed by Benedette Cuffari, M.Sc. In a recent study published in Nature Communications, researchers evaluate the impact of tumor-derived growth and differentiation factor-15 on leukocyte function-associated antigen 1 -based T-lymphocyte recruitment and responses to anti-programmed cell death protein-1 immunotherapy.
The current study involved the production of recombinant GDF-15 in human embryonic kidney 293T cells and the development of an anti-human GDF-15 antibody in C57BL/6J GDF-15-/- mice. The antibody was validated for binding affinity by surface plasmon resonance , whereas specificity was evaluated by tissue cross-reactivity studies. The experiments involved the inoculation of MC38 colon tumor cells, Panc02 pancreatic cancer cells, and murine EMT6 breast cancer cells in C57BL mice.
Eighty-six patients with histologically confirmed oropharyngeal squamous cell carcinoma were also included in the study. Additionally, surplus sera were obtained at the initiation of ipilimumab therapy from 37 patients with stage IV melanoma, as well as 34 patients with melanoma at the initiation of pembrolizumab therapy.
Furthermore, ligand-complex-based binding assays and monoclonal antibody 24 anti-active LFA-1 conformation-specific staining were performed, followed by dSTORM super-resolution microscopy for analysis of active and inactive LFA-1. In addition to its established role in malignancy-associated cachexia and anorexia, GDF-15 appears to be a mediator of T-cell extravasation into tumor microenvironments, thus providing more justification for the development of therapeutic antibodies against GDF-15. Tumor-derived GDF-15 inhibited the LFA-1/intercellular adhesion molecule 1 axis in T-cells and T-cell migration into tumors.
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