Systemic clinical tumor regressions and potentiation of PD1 blockade with in situ vaccination

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

“…49 This knowledge has fostered the recent enthusiasm for administering FLT3LG together with radiotherapy as an in situ vaccination strategy in combination with immune checkpoint-blocking therapy, in order to obtain systemic therapeutic effects. 34 In the present analysis, we found that intratumoural delivery of oxaliplatin caused FLT3LG release into the circulation, supporting the notion that oxaliplatin may promote an intratumoural immune response that specifically recruits dendritic cells to present antigens released by the dying tumour cells to cytotoxic lymphocytes, ultimately providing systemic immunity. The likely freedom from recurrent metastasis in CLM-ablated patients who had experienced a rapid initial rise in circulating FLT3LG during the oxaliplatin-HAI therapy appears to agree with the theory that FLT3LG production reflects an innate immune response, specifically comprising natural killer cells, within the tumour microenvironment.…”

“…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.…”

Immunology‐Guided Biomaterial Design for Mucosal Cancer Vaccines

“…Consequently, this subset should be of major consideration as a target when designing cancer vaccines. For example, delivery of Fms‐like tyrosine kinase 3 ligand (Flt3L) was recently demonstrated to promote accumulation of intratumoral, cross‐presenting DC, resulting in tumor‐specific CD8 + T cell response …”