# Predictive potential of patient-specific immunological characteristics in solid cancers: circulating monocytes, myeloid-derived suppressor cells, T cells, and the T-cell receptor repertoire

## TL;DR

This study shows that specific types of monocytes in the blood can predict survival and treatment response in cancer patients, independent of the tumor type.

## Contribution

The study identifies monocyte subsets as potential tumor-agnostic, patient-specific biomarkers for predicting therapy response in solid cancers.

## Key findings

- High non-classical monocytes at baseline were linked to improved progression-free survival and response to chemotherapy.
- Intermediate monocytes increased in ICI responders compared to non-responders, suggesting a role in predicting checkpoint inhibitor response.
- TCR diversity, T cells, and MDSCs showed no association with patient outcomes across therapies.

## Abstract

Response prediction to immune checkpoint inhibitors (ICIs) relies on tumor-specific biomarkers, while patient-specific characteristics are underrepresented. Therefore, we explored patient-specific immunological characteristics, including peripheral monocytes, myeloid-derived suppressor cells (MDSCs), T cells, and the T-cell receptor (TCR) repertoire, to investigate associations with survival and therapy response.

Patients with solid tumors were prospectively recruited to explore the association of absolute lymphocyte and monocyte counts, leukocyte-to-lymphocyte ratio (LLR), and monocyte-to-lymphocyte ratio (MLR) with overall survival (OS). Monocytes, MDSCs, T cells, and the TCR repertoire were characterized before therapy start (baseline) and, if available, at first radiological restaging (follow-up). We analyzed their association with radiological therapy response using current guidelines, OS, and progression-free survival (PFS).

A total of 1063 patients were included. High LLR [≥3.92; hazard ratio (HR) 1.48, 95% confidence interval (CI) 1.21-1.82, P < 0.001] and high MLR (≥0.31; HR 1.43, 95% CI 1.16-1.76, P < 0.001) at baseline were associated with worse OS. In 108 patients, high non-classical monocytes (NCMs) at baseline were linked to improved PFS (≥8.94%; HR 0.41, 95% CI 0.18-0.91, P = 0.03), indicating a prognostic effect independent of therapy type. High NCMs at baseline were associated with response to chemotherapy (P = 0.03), but not to ICI therapy (P = 0.47). Longitudinal analyses revealed an increase in intermediate monocytes (IMs) among ICI responders compared with ICI non-responders (P = 0.01). IMs were unaltered in chemotherapy-treated patients (P = 0.69). The TCR repertoire, T cells, and MDSCs revealed no differences between responders and non-responders, regardless of therapy.

In our study, monocyte subsets were associated with survival and therapy response. These results highlight the potential of monocyte subsets to serve as patient-specific, tumor-agnostic biomarkers that may help predict therapy response.

•IMs and NCMs were associated with survival and therapy response to checkpoint inhibition.•TCR diversity, T cells, and MDSCs were not linked to patient outcomes.•Longitudinal monitoring of peripheral blood monocyte subsets might serve as a patient-specific, tumor-agnostic biomarker.

IMs and NCMs were associated with survival and therapy response to checkpoint inhibition.

TCR diversity, T cells, and MDSCs were not linked to patient outcomes.

Longitudinal monitoring of peripheral blood monocyte subsets might serve as a patient-specific, tumor-agnostic biomarker.