RNAseq transcriptome of draining lymph node (LN) and tumor of MC38 murine tumors treated with cryoablation and chitosan/IL-12

Focal ablation technologies are routinely used in the clinical management
of inoperable solid tumors but often result in incomplete ablations
leading to high recurrence rates. Adjuvant therapies capable of safely
eliminating residual tumor cells are therefore of great clinical interest.
Interleukin 12 (IL-12) is a potent antitumor cytokine that can be
localized intratumorally through coformulation with viscous biopolymers
including chitosan (CS) solutions. The objective of this research was to
determine if localized immunotherapy with CS/IL-12 could prevent tumor
recurrence after cryoablation (CA). Tumor recurrence, overall survival,
and protective immunity were assessed. Systemic immunity was evaluated in
spontaneously metastatic and bilateral tumor models. Temporal bulk RNA
sequencing was performed on tumor and draining lymph node samples. In
multiple murine tumor models, the addition of CS/IL-12 to CA reduced
recurrence rates by 30–55%. Altogether, this cryo-immunotherapy induced
complete durable regression of large tumors in 80–100% of treated animals.
Mice treated with CA plus adjuvant CS/IL-12 were partially or completely
protected from tumor rechallenge. Systemically, CS/IL-12 prevented lung
metastases when delivered as a neoadjuvant to CA. However, CA plus
CS/IL-12 had minimal antitumor activity against established, untreated
abscopal tumors. Adjuvant anti-PD-1 therapy delayed the growth of abscopal
tumors. Transcriptome analyses revealed early immunological changes in the
dLN, followed by a significant increase in gene expression associated with
immune suppression and regulation. Cryo-immunotherapy with localized
CS/IL-12 reduces recurrences and enhances the elimination of large primary
tumors. This focal combination therapy also induces significant systemic
antitumor immunity although further studies are necessary.