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.

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.

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