Abstract
Despite encouraging results with immune checkpoint inhibition (ICI), a large fraction of cancer patients still does not achieve clinical benefit. Finding predictive markers in the complexity of the tumor microenvironment is a challenging task and often requires invasive procedures. In our study, we looked for putative variables related to treatment benefit among immune cells in peripheral blood across different tumor types treated with ICIs. For that, we included 33 patients with different solid tumors referred to our clinical unit for ICI. Peripheral blood mononuclear cells were isolated at baseline, 6 and 20 weeks after treatment start. Characterization of immune cells was carried out by multi-color flow cytometry. Response to treatment was assessed radiologically by RECIST 1.1. Clinical outcome correlated with a shift towards an effector-like T cell phenotype, PD-1 expression by CD8+T cells, low levels of myeloid-derived suppressor cells and classical monocytes. Dendritic cells seemed also to play a role in terms of survival. From these findings, we hypothesized that patients responding to ICI had already at baseline an immune profile, here called ‘favorable immune periphery’, providing a higher chance of benefitting from ICI. We elaborated an index comprising cell types mentioned above. This signature correlated positively with the likelihood of benefiting from the treatment and ultimately with longer survival. Our study illustrates that patients responding to ICI seem to have a pre-existing immune profile in peripheral blood that favors good outcome. Exploring this signature can help to identify patients likely to achieve benefit from ICI.
Highlights
The advent of immune checkpoint inhibitors (ICI) as an effective therapeutic modality in oncology has come under spotlight during the last decades, mainly after the first clinical trial showing positive impact of ipilimumab for treatment of patients with metastatic melanoma [1].Despite encouraging results [2,3,4], a considerable fraction of patients undergoing immune checkpoint inhibition (ICI) still do not benefit from the treatment [5] and primary or acquired ICI resistance is a significant problem that patients and clinicians face on a daily basis
We present data indicating that despite possible differences in the PBMC’s composition across patients with different tumor types, there is an underlying preexisting immune signature among patients likely to benefit from ICI
Studies trying to find predictive biomarkers for response have broadly focused on variables spanning from genetic determinants, cell composition in the tumor microenvironment to markers in the peripheral blood and microbiome [22, 24]
Summary
The advent of immune checkpoint inhibitors (ICI) as an effective therapeutic modality in oncology has come under spotlight during the last decades, mainly after the first clinical trial showing positive impact of ipilimumab for treatment of patients with metastatic melanoma [1].Despite encouraging results [2,3,4], a considerable fraction of patients undergoing ICI still do not benefit from the treatment [5] and primary or acquired ICI resistance is a significant problem that patients and clinicians face on a daily basis. Efforts trying to predict patients likely to respond to ICI are numerous and comprise a myriad of variables spanning from isolated genetic features (e.g. tumor mutational burden, neoepitope load, transcriptomic signatures) [6,7,8,9] to multiparametric approaches looking into the tumor microenvironment (TME)’s cellular composition (e.g. immunoscore [10]). Common ground for these methods is the fact that they are tumor tissue-centered, which is reasonable since tumor site harbors the ‘battlefield’ where interactions between cancer and immune system unfold. Another disadvantage is that invasive procedures are required to keep track of changes happening during ICI, which is not always feasible
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