Targeting tumor extracellular matrix activates the tumor-draining lymph nodes

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 a...

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Bibliographic Details
Published in:Cancer Immunology, Immunotherapy Immunotherapy, 2022-12, Vol.71 (12), p.2957-2968
Main Authors: Najibi, Alexander J., Shih, Ting-Yu, Zhang, David K. Y., Lou, Junzhe, Sobral, Miguel C., Wang, Hua, Dellacherie, Maxence O., Adu-Berchie, Kwasi, Mooney, David J.
Format: Article
Language:English
Subjects:
Animals
Antigen presentation
Antigens, Neoplasm
Cancer Research
Cancer Vaccines
CD103 antigen
CD8 antigen
Collagen
Cryogels
Dendritic Cells
Enzymes
Extracellular Matrix
Humans
Hyaluronic acid
Hyaluronoglucosaminidase
Immunology
Immunotherapy
Laboratories
Lymph Nodes
Lymphatic system
Lymphocytes
Lymphocytes T
Macrophages
Medicine
Medicine & Public Health
Melanoma
Melanoma, Experimental
Metastases
Oncology
Original
Original Article
Ovalbumin
Physical restraints
Prostate cancer
Rheology
Tumors
Vaccines
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Summary: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.
ISSN:0340-7004
1432-0851
DOI:10.1007/s00262-022-03212-6