Growth factor supportive care for chemotherapy-induced neutropenia suppresses antitumour immunity in checkpoint blockade-responsive pancreatic cancer.

Abstract

Introduction: Growth factors, including granulocyte colony-stimulating factor (G-CSF; pegfilgrastim, filgrastim), are used for prophylaxis or treatment of chemotherapy-induced neutropenia, yet their effects on antitumour immunity remain incompletely understood. We previously found that serum from patients with pancreatic ductal adenocarcinoma (PDAC) treated with multiagent chemotherapy plus G-CSF drove differentiation of T cell-suppressive monocytes in vitro, suggesting that supportive care interventions may shape immune responses in this disease.

Methods: We evaluated the immunologic and therapeutic impact of G-CSF in two murine PDAC models that differ in their baseline frequencies of infiltrating T cells and in their responsiveness to checkpoint blockade immunotherapy.

Results: In poorly immunogenic, T-cell-low tumours, use of G-CSF did not affect tumour growth or response to chemo- or immunotherapy, although neutrophil recovery was improved in mice receiving FOLFIRINOX and G-CSF compared to chemotherapy alone. In immunogenic tumours with a robust endogenous T-cell response, combination anti-PD1 and anti-CTLA-4 therapy resulted in durable tumour clearance. Combination with G-CSF diminished the effectiveness of checkpoint blockade and resulted in significantly fewer cured mice.

Conclusion: G-CSF, commonly used for supportive care with FOLFIRINOX and other chemotherapy regimens, induces systemic immune suppression that can reduce the efficacy of T-cell-targeting immunotherapies.