Targeting tumor extracellular matrix activates the tumor-draining lymph nodes

Area of Science:

• Immunology
• Oncology
• Biochemistry

Background:

• The tumor extracellular matrix (ECM) influences immune cell infiltration and T cell priming.
• Modulating the ECM could impact antitumor immunity.

Purpose of the Study:

• To investigate how intratumoral enzyme treatment (ET) affects immune populations in B16 melanoma tumors and tumor-draining lymph nodes (tdLNs).
• To assess the potential of ET to enhance T cell responses and support cancer immunotherapies.

Main Methods:

• B16 melanoma tumors were treated intratumorally with hyaluronidase, an ECM-depleting enzyme.
• Immune cell populations (T cells, DCs, macrophages) in tumors and tdLNs were analyzed.
• Antigen presentation of ovalbumin (OVA) and OVA-specific CD8+ T cell responses were measured.
• ET was combined with a cryogel-based cancer vaccine to evaluate systemic immune responses.

Main Results:

• ET increased the abundance of CD103+ dendritic cells (DCs) in tdLNs.
• ET enhanced antigen presentation of a model tumor antigen (OVA).
• ET elicited local OVA-specific CD8+ T cell responses.
• Combined ET and cancer vaccine treatment increased systemic antigen-specific CD8+ T cell responses.

Conclusions:

• Intratumoral enzyme treatment disrupts the tumor ECM, promoting immune cell infiltration and activation.
• ET enhances dendritic cell function and T cell priming in tumor-draining lymph nodes.
• ET shows potential as an adjuvant therapy to improve the efficacy of cancer vaccines and immunotherapies.