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Combination immunotherapy with TLR agonists and checkpoint inhibitors suppresses head and neck cancer.

ABSTRACT: Checkpoint inhibitors have demonstrated efficacy in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). However, the majority of patients do not benefit from these agents. To improve the efficacy of checkpoint inhibitors, intratumoral (i.t.) injection with innate immune activators, TLR7 and TLR9 agonists, were tested along with programmed death-1 receptor (PD-1) blockade. The combination therapy suppressed tumor growth at the primary injected and distant sites in human papillomavirus-negative (HPV-negative) SCC7 and MOC1, and HPV-positive MEER syngeneic mouse models. Abscopal effects and suppression of secondary challenged tumor suggest that local treatment with TLR agonists in combination with anti-PD-1 provided systemic adaptive immunity. I.t. treatment with a TLR7 agonist increased the ratio of M1 to M2 tumor-associated macrophages (TAMs) and promoted the infiltration of tumor-specific IFN?-producing CD8+ T cells. Anti-PD-1 treatment increased T cell receptor (TCR) clonality of CD8+ T cells in tumors and spleens of treated mice. Collectively, these experiments demonstrate that combination therapy with i.t. delivery of TLR agonists and PD-1 blockade activates TAMs and induces tumor-specific adaptive immune responses, leading to suppression of primary tumor growth and prevention of metastasis in HNSCC models.

SUBMITTER: Sato-Kaneko F

PROVIDER: S-EPMC5621908 | biostudies-other | 2017 Sep

REPOSITORIES: biostudies-other

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Combination immunotherapy with TLR agonists and checkpoint inhibitors suppresses head and neck cancer.

Sato-Kaneko Fumi F Yao Shiyin S Ahmadi Alast A Zhang Shannon S SS Hosoya Tadashi T Kaneda Megan M MM Varner Judith A JA Pu Minya M Messer Karen S KS Guiducci Cristiana C Coffman Robert L RL Kitaura Kazutaka K Matsutani Takaji T Suzuki Ryuji R Carson Dennis A DA Hayashi Tomoko T Cohen Ezra Ew EE

JCI insight 20170921 18

Checkpoint inhibitors have demonstrated efficacy in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). However, the majority of patients do not benefit from these agents. To improve the efficacy of checkpoint inhibitors, intratumoral (i.t.) injection with innate immune activators, TLR7 and TLR9 agonists, were tested along with programmed death-1 receptor (PD-1) blockade. The combination therapy suppressed tumor growth at the primary injected and distant sites in ...[more]

PMID: 28931759

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Dataset Information

Combination immunotherapy with TLR agonists and checkpoint inhibitors suppresses head and neck cancer.

Publications

Combination immunotherapy with TLR agonists and checkpoint inhibitors suppresses head and neck cancer.

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