Br J Cancer: Autoimmunity induced by immune checkpoint blocking therapy is related to the prognosis of metastatic melanoma and a unique T cell expression profile

Immune Checkpoint Blocking (ICB) therapy is a type of treatment that mediates T cell activity to increase the anti- tumor immune response.
It has been used in the treatment of metastatic melanoma (MM).
Current ICB standard treatment strategies include anti-PD1 monotherapy (nivolumab or pembrolizumab, sICB) or anti-CTLA-4/anti-PD1 (ipilimumab and nivolumab, cICB) combination therapy.

ICB can activate CD8+ T cells, which in turn causes resistance and immune-related adverse reactions (irAEs).
However, the relationship between irAEs and baseline parameters and clinical outcomes is unclear.

The purpose of this study was to retrospectively evaluate the survival of irAEs and patients in independent cohorts of patients with metastatic melanoma who received monotherapy or combination therapy (N=144) and secondary (N=211).
The RNA from CD8+ T cells before and after treatment was sequenced, and the expression of differential genes was evaluated according to the irAE situation.

Kaplan-Meier curve analysis of overall survival (OS) and progression-free survival (PFS) of patients

The results showed that 58.
3% of patients had early irAE, which was related to longer progression-free (PFS) and overall survival (OS) in the two cohorts.
The median survival of patients without irAEs was 16.
6 months.

The expression of different genes in CD8+ T cells

The number of monocytes and neutrophils before treatment, rather than BMI value, is a supplementary predictor of the patient's clinical outcome.
According to the occurrence of irAE, the researchers observed the differential expression of many gene pathway members in CD8+ T cells.
In patients without irAE, the expression level of CXCR1 was up-regulated before and after treatment.

All in all, the results of this study show that the early occurrence of irAE after ICB treatment is related to the better survival of MM patients.