Targeting tumor extracellular matrix activates the tumor-draining lymph nodes

靶向肿瘤细胞外基质激活肿瘤引流淋巴结

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作者:Alexander J Najibi, Ting-Yu Shih, David K Y Zhang, Junzhe Lou, Miguel C Sobral, Hua Wang, Maxence O Dellacherie, Kwasi Adu-Berchie, David J Mooney

Abstract

Disruption of the tumor extracellular matrix (ECM) may alter immune cell infiltration into the tumor and antitumor T cell priming in the tumor-draining lymph nodes (tdLNs). Here, we explore how intratumoral enzyme treatment (ET) of B16 melanoma tumors with ECM-depleting enzyme hyaluronidase alters adaptive and innate immune populations, including T cells, DCs, and macrophages, in the tumors and tdLNs. ET increased CD103+ DC abundance in the tdLNs, as well as antigen presentation of a model tumor antigen ovalbumin (OVA), eliciting local OVA-specific CD8+ T cell responses. Delivered in combination with a distant cryogel-based cancer vaccine, ET increased the systemic antigen-specific CD8+ T cell response. By enhancing activity within the tdLN, ET may broadly support immunotherapies in generating tumor-specific immunity.

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