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The tumor-sentinel lymph node immuno-migratome reveals CCR7⁺ dendritic cells drive response to sequenced immunoradiotherapy

Tumor draining lymph nodes are essential for immunotherapy efficacy in head and neck squamous cell carcinoma (HNSCC). Here, the authors show that sequential tumor-directed radiotherapy and PD-1 inhibition and migratory CCR7+ dendritic cells are required for complete and durable tumor responses in HNSCC.

Robert Saddawi-Konefka
Riyam Al Msari
Joseph A. Califano
ResearchOpen Access17 Jul 2025
Nature Communications

Volume: 16, P: 1-19
Longitudinal liquid biopsy identifies an early predictive biomarker of immune checkpoint blockade response in head and neck squamous cell carcinoma

The response to immune checkpoint blockade in head and neck cancer has been heterogenous. Here, the authors utilise longitudinal sampling of a head and neck squamous cell carcinoma model to identify biomarkers of response.

Binbin Wang
Robert Saddawi-Konefka
Eytan Ruppin
ResearchOpen Access01 Sept 2025
Nature Communications

Volume: 16, P: 1-15
In vivo CRISPR screening in head and neck cancer reveals Uchl5 as an immunotherapy target

UCHL5 is a deubiquitinating enzyme that cleaves Lys-48-linked polyubiquitin chains. Here, the authors discover through in-vivo CRISPR-Cas9 screens that Uchl5 is involved in immune evasion and modulation of extracellular matrix deposition in head and neck squamous cell carcinoma.

Cong Fu
Robert Saddawi-Konefka
Robert T. Manguso
ResearchOpen Access29 Sept 2025
Nature Communications

Volume: 16, P: 1-18
The GPCR–Gα_s–PKA signaling axis promotes T cell dysfunction and cancer immunotherapy failure

Here, the authors use computational screening and a chemogenetic analysis of transgenic mice to show that Gα_s-coupled G-protein-coupled receptors on exhausted CD8⁺ T cells are involved in suppression of effector functions and inhibition of the protective effects of immune checkpoint immunotherapy.

Victoria H. Wu
Bryan S. Yung
J. Silvio Gutkind
Research12 Jun 2023
Nature Immunology

Volume: 24, P: 1318-1330
Lymphatic-preserving treatment sequencing with immune checkpoint inhibition unleashes cDC1-dependent antitumor immunity in HNSCC

Response rates to immune checkpoint inhibitors (ICI) in patients with head and neck squamous cell carcinoma (HNSCC) remain low. Here the authors show that ablative treatment of tumor-draining regional lymphatics, a standard of care approach in patients, impairs the tumor response to ICI in preclinical HNSCC models.

Robert Saddawi-Konefka
Aoife O’Farrell
J. Silvio Gutkind
ResearchOpen Access25 Jul 2022
Nature Communications

Volume: 13, P: 1-19
Disruption of the HER3-PI3K-mTOR oncogenic signaling axis and PD-1 blockade as a multimodal precision immunotherapy in head and neck cancer

There is an unmet need to improve the response to immune checkpoint blockade in patients with head and neck squamous cell carcinoma (HNSCC). Here the authors show that aberrant HER3 activation sustains the proliferation of PIK3CA wild type HNSCC cells and that HER3 inhibition increases response to PD-1 blockade in HNSCC preclinical models.

Zhiyong Wang
Yusuke Goto
J. Silvio Gutkind
ResearchOpen Access22 Apr 2021
Nature Communications

Volume: 12, P: 1-13
Interleukin-17D and Nrf2 mediate initial innate immune cell recruitment and restrict MCMV infection

Ruth Seelige
Robert Saddawi-Konefka
Jack D. Bui
ResearchOpen Access12 Sept 2018
Scientific Reports

Volume: 8, P: 1-14

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The tumor-sentinel lymph node immuno-migratome reveals CCR7⁺ dendritic cells drive response to sequenced immunoradiotherapy

Longitudinal liquid biopsy identifies an early predictive biomarker of immune checkpoint blockade response in head and neck squamous cell carcinoma

In vivo CRISPR screening in head and neck cancer reveals Uchl5 as an immunotherapy target

The GPCR–Gα_s–PKA signaling axis promotes T cell dysfunction and cancer immunotherapy failure

Lymphatic-preserving treatment sequencing with immune checkpoint inhibition unleashes cDC1-dependent antitumor immunity in HNSCC

Disruption of the HER3-PI3K-mTOR oncogenic signaling axis and PD-1 blockade as a multimodal precision immunotherapy in head and neck cancer

Interleukin-17D and Nrf2 mediate initial innate immune cell recruitment and restrict MCMV infection

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The tumor-sentinel lymph node immuno-migratome reveals CCR7⁺ dendritic cells drive response to sequenced immunoradiotherapy

Longitudinal liquid biopsy identifies an early predictive biomarker of immune checkpoint blockade response in head and neck squamous cell carcinoma

In vivo CRISPR screening in head and neck cancer reveals Uchl5 as an immunotherapy target

The GPCR–Gαs–PKA signaling axis promotes T cell dysfunction and cancer immunotherapy failure

Lymphatic-preserving treatment sequencing with immune checkpoint inhibition unleashes cDC1-dependent antitumor immunity in HNSCC

Disruption of the HER3-PI3K-mTOR oncogenic signaling axis and PD-1 blockade as a multimodal precision immunotherapy in head and neck cancer

Interleukin-17D and Nrf2 mediate initial innate immune cell recruitment and restrict MCMV infection

Search

Quick links

The GPCR–Gα_s–PKA signaling axis promotes T cell dysfunction and cancer immunotherapy failure