Systemic immune response induced by oxaliplatin-based neoadjuvant therapy favours survival without metastatic progression in high-risk rectal cancer

Abstract

In high-risk rectal cancer, oxaliplatin-containing neoadjuvant therapy may promote an immune response that favours survival without metastatic progression.

Antitumour immunity invoked by hepatic arterial infusion of first‐line oxaliplatin predicts durable colorectal cancer control after liver metastasis ablation: 8–12 years of follow‐up

“…36 However, genuine cure of the metastatic disease was additionally contingent on therapeutic conversion to resectability as a result of the 'classic' cytotoxic effect of chemotherapy. 32 Within this frame of reference, it is tempting to speculate whether patients in the present study who presented an insufficient FLT3LG accretion, yet achieved CLM resectability, might have obtained long-term survival from the addition of immune checkpoint-blocking therapy. 31 Those who had an immediate rise in circulating FLT3LG during the neoadjuvant course were cured after pelvic tumour clearance enabled by sufficient tumour regression after the cytotoxic therapy.…”

“…31 Those who had an immediate rise in circulating FLT3LG during the neoadjuvant course were cured after pelvic tumour clearance enabled by sufficient tumour regression after the cytotoxic therapy. 32 Within this frame of reference, it is tempting to speculate whether patients in the present study who presented an insufficient FLT3LG accretion, yet achieved CLM resectability, might have obtained long-term survival from the addition of immune checkpoint-blocking therapy.…”

“…In order to improve the selection of patients with isolated, primarily unresectable CLM for curative-intent ablation after chemotherapy, a better understanding of the underlying biology and the development of molecular markers for long-term therapeutic benefit are needed. 41 We noted that patients who during first-line oxaliplatin-HAI presented a rapid and substantial rise in circulating FLT3LG over the initial treatment, regarded as a marker of invoked tumour-defeating immunity, [32][33][34] and at treatment completion could proceed to CLM ablation, were alive at final follow-up 8-12 years later. Essentially, all study patients experienced serum FLT3LG increase after start of the therapy.…”

“…26,27 The majority of CRC cases are not inherently immunogenic 28,29 but might, if transformed to such a state by oxaliplatin, be subject to improved systemic immune surveillance with reduced risk of disease progression. 32 The FLT3LG is a potent growth factor for antigen-presenting dendritic cells 33,34 and when administered to patients with metastatic CRC, has led to expansion of the dendritic cell population both locally in tumour and systematically. Patients who experienced a pronounced rise in serum levels of the fms-related tyrosine kinase 3 ligand (FLT3LG) during the neoadjuvant treatment course, interpreted as ICD induction, had significantly better progression-free survival than those without such response, implying that an advantageous systemic immune response might have been invoked by oxaliplatin.…”

“…Patients who experienced a pronounced rise in serum levels of the fms-related tyrosine kinase 3 ligand (FLT3LG) during the neoadjuvant treatment course, interpreted as ICD induction, had significantly better progression-free survival than those without such response, implying that an advantageous systemic immune response might have been invoked by oxaliplatin. 32 The FLT3LG is a potent growth factor for antigen-presenting dendritic cells 33,34 and when administered to patients with metastatic CRC, has led to expansion of the dendritic cell population both locally in tumour and systematically. 35 In melanoma, which is the archetype immunogenic tumour entity, it was recently demonstrated that intratumoural natural killer cells are the source of the dendritic cell-stimulatory FLT3LG.…”