TY - JOUR
T1 - Targeting tumor extracellular matrix activates the tumor-draining lymph nodes
AU - Najibi, Alexander J.
AU - Shih, Ting Yu
AU - Zhang, David K.Y.
AU - Lou, Junzhe
AU - Sobral, Miguel C.
AU - Wang, Hua
AU - Dellacherie, Maxence O.
AU - Adu-Berchie, Kwasi
AU - Mooney, David J.
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
KW - Adaptive immunity
KW - Cancer vaccine
KW - Tumor extracellular matrix
KW - Tumor-draining lymph nodes
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UR - http://www.scopus.com/inward/citedby.url?scp=85129566491&partnerID=8YFLogxK
U2 - 10.1007/s00262-022-03212-6
DO - 10.1007/s00262-022-03212-6
M3 - Article
C2 - 35524791
AN - SCOPUS:85129566491
SN - 0340-7004
VL - 71
SP - 2957
EP - 2968
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
IS - 12
ER -