Systemic Blood Immune Cell Populations as Biomarkers for the Outcome of Immune Checkpoint Inhibitor Therapies

Abstract

The development of cancer immunotherapy in the last decade has followed a vertiginous rhythm. Nowadays, immune checkpoint inhibitors (ICI) which include anti-CTLA4, anti-PD-1 and anti-PD-L1 antibodies are in clinical use for the treatment of numerous cancers. However, approximately only a third of the patients benefit from ICI therapies. Many efforts have been made for the identification of biomarkers allowing patient stratification into potential responders and progressors before the start of ICI therapies or for monitoring responses during treatment. While much attention is centered on biomarkers from the tumor microenvironment, in many cases biopsies are not available. The identification of systemic immune cell subsets that correlate with responses could provide promising biomarkers. Some of them have been reported to influence the response to ICI therapies, such as proliferation and activation status of CD8 and CD4 T cells, the expression of immune checkpoints in peripheral blood cells and the relative numbers of immunosuppressive cells such as regulatory T cells and myeloid-derived suppressor cells. In addition, the profile of soluble factors in plasma samples could be associated to response or tumor progression. Here we will review the cellular subsets associated to response or progression in different studies and discuss their accuracy in diagnosis.

PD-1 and PD-L1 Expression on Circulating Lymphocytes as a Marker of Epstein-Barr Virus Reactivation-Associated Proliferative Glomerulonephritis

“…As a result, TCR signaling during antigen presentation to naïve T cells is inhibited [13]. Therefore, in the case of persistent auto-or exo-antigenic stimulation, the PD-1/PD-L1/2 pathway plays a crucial inhibitory role [14][15][16].…”

Enhancing clinical and immunological effects of anti-PD-1 with belapectin, a galectin-3 inhibitor

“…In these patients, the baseline percentage of circulating MDSCs inversely correlated with response to aCTLA-4 and OS. [51][52][53] Limited data exist for the effect of pembrolizumab on MDSCs. One study has shown that the baseline percentage of circulating MDSCs inversely correlated with response and OS in melanoma patients treated with nivolumab.…”

Combined Gemcitabine and Immune-Checkpoint Inhibition Conquers Anti-PD-L1 Resistance in Low-Immunogenic Mismatch Repair-Deficient Tumors

“…The notion that we did not see any differences in numbers of circulating and splenic MDSCs in any treatment group matches with recent studies [ 41 ] and may explain the final relapse of Mlh1 −/− tumors. Generally, a high frequency of memory cells and low numbers of immunosuppressive cells are indicative of a good response, though individual differences exist [ 42 ]. The Mlh1 −/− mouse model is representative for immunosuppressive subtypes, thus, converting immune regulatory cells into pro-inflammatory cell types seem challenging.…”