A deficient MIF-CD74 signaling pathway may play an important role in immunotherapy-induced hyper-progressive disease

With the advent of immune checkpoint inhibitors (ICIs) therapies, a major breakthrough has been made in cancer treatment. However, instead of good results, some patients experienced a deterioration of their disease. This unexpected result is termed as hyper-progressive disease (HPD). The biology of HPD is currently not fully understood.

Isolation of CD3⁺ cells from peripheral blood mononuclear cells (PBMC) in healthy control, tumor patients receiving immunotherapy with or without immunotherapy-induced HPD, then conducted single-cell RNA sequencing (scRNA-seq).

By analyzing scRNA-seq data, we identified 15 cell clusters. We observed developed-exhausted CD4⁺ T cells and regulatory T cells (Tregs) increasingly enriched in HPD group. Meanwhile, some effector T cells were decreased in HPD. The imbalance potentially contributes to the occurrence of HPD and poor clinical prognosis. In addition, we analyzed ligand-receptor interactions between subsets. The ligand-receptor interaction "CD74-MIF" was absent in HPD. However, in vitro experiment, we found that CD74 regulated effector function of effector CD8⁺ T cells. Overall, the article provides a primary study of immune profile in HPD.