Circulating mucosal-associated invariant T cells identify patients responding to anti-PD-1 therapy

Abstract

Immune checkpoint inhibitors are used for treating patients with metastatic melanoma. Since the response to treatment is variable, biomarkers are urgently needed to identify patients who may benefit from such therapy. Here, we combine single-cell RNA-sequencing and multiparameter flow cytometry to assess changes in circulating CD8+ T cells in 28 patients with metastatic melanoma starting anti-PD-1 therapy, followed for 6 months: 17 responded to therapy, whilst 11 did not. Proportions of activated and proliferating CD8+ T cells and of mucosal-associated invariant T (MAIT) cells are significantly higher in responders, prior to and throughout therapy duration. MAIT cells from responders express higher level of CXCR4 and produce more granzyme B. In silico analysis support MAIT presence in the tumor microenvironment. Finally, patients with >1.7% of MAIT among peripheral CD8+ population show a better response to treatment. Our results thus suggest that MAIT cells may be considered a biomarker for patients responding to anti-PD-1 therapy.

Cell Death in Coronavirus Infections: Uncovering Its Role during COVID-19

“…Moreover, circulating monocytes showed an important expression of immune checkpoints proteins (ICPs) with the characteristics of being inhibitory such as programmed death-1 (PD-1) and its ligand PD-L1 [ 23 ]. The expression and interaction of these molecules, which occurs in cases of exaggerated activation, blocks the effector action of T cells leading to the inhibition of immune response [ 27 ].…”

Recent Advances and Future Prospects in Immune Checkpoint (ICI)-Based Combination Therapy for Advanced HCC

“…Another study in melanoma patients revealed a specific subset of T-cells correlated with ICI responders [94]. Twenty-eight patients with melanoma received anti-PD-1 ICI.…”

MAIT Cells: Partners or Enemies in Cancer Immunotherapy?

“…Other studies of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) observed that tumor-residing MAIT cells upregulated expression of IFN-γ, GZM K, GZM A and GZM M following PD-1 blockade [80]. Additionally, higher MAIT cell proportions were recently found to correlate with better responses to anti-PD-1 immunotherapy, with MAIT cells from responders having a greater cytotoxic function [28]. These results suggest that the PD-1 pathway may be involved in mediating MAIT cell dysfunction in certain cancers, and that, in addition to its canonical role in antitumor immunity, anti-PD-1 therapy may restore the expression of certain cytotoxic genes.…”

“…As such, the results should be interpreted with caution when assessing the applicability to humans. When MAIT cells were studied in melanoma patients on anti-PD-1 therapy, high MAIT cell proportions were found in those responding to PD-1 therapy as opposed to patients who were not responding [28] (Table 1). MAIT cells from responders also had higher levels MAIT cells in the melanoma lesions than non-responders, as well as increased levels of GZMB [28] (Table 1), indicating that MAIT cells from responders have higher cytotoxic functions while circulating and infiltrating the tumor site.…”