Intratumoral Injection of Cytotoxic Drugs Plus Hapten Elicits Significant Immune Responses in Sentinel Lymph Nodes: Implications for Cancer Immunotherapy.

Abstract

Objectives: Studying the sentinel lymph nodes (SLNs) to define the metastasis and the mechanisms of abscopal effect.

Method: Using scRNA-seq to investigate the cellular and genomic changes of SLNs before or after treatment of the primar pancreatic carcinoma site by intratumoral injection of cytotoxic chemotherapy drugs plus hapten.

Result: A very significant decrease of SLN carcinoma cells, but increased macrophages, monocytes, CD8 T-effector cells, and fibroblasts. At the genomic and functional levels, the above treatment increased the ability of angiogenesis, epithelial mesenchymal transition (EMT), and cancer-associated fibroblast (CAF) signaling. In addition, matricellular proteins were upregulated.

Alternative conclusion: Our study demonstrated a marked reduction in carcinoma cells within SLNs following treatment, alongside a notable increase in inflammatory and stromal cells, which suggested a dynamic reorganization of the lymph node microenvironment rather than straightforward tumor growth. The absence of significant enlargement of SLNs, despite the increase in cellular density, may be attributed to the remodeling effects induced by the treatment. The observed upregulation of angiogenic factors, EMT pathways, and CAF signaling highlighted a complex interaction between tumor and immune responses. These findings provided new insights into the abscopal effect, revealing how targeted therapies can modulate lymph node microenvironments to enhance local immune responses and potentially improve systemic antitumor efficacy.