Galectin-1–driven T cell exclusion in the tumor endothelium promotes immunotherapy resistance

Immune checkpoint inhibitors (ICIs), although promising, have variable benefit in head and neck cancer (HNC). We noted that tumor galectin-1 (Gal1) levels were inversely correlated with treatment response and survival in patients with HNC who were treated with ICIs. Using multiple HNC mouse models, we show that tumor-secreted Gal1 mediates immune evasion by preventing T cell migration into the tumor. Mechanistically, Gal1 reprograms the tumor endothelium to upregulate cell-surface programmed death ligand 1 (PD-L1) and galectin-9. Using genetic and pharmacological approaches, we show that Gal1 blockade increases intratumoral T cell infiltration, leading to a better response to anti-PD1 therapy with or without radiotherapy. Our study reveals the function of Gal1 in transforming the tumor endothelium into an immune-suppressive barrier and that its inhibition synergizes with ICIs.
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research

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Source: International Journal of Hyperthermia - Category: Internal Medicine Tags: Int J Hyperthermia Source Type: research
Condition:   Head and Neck Neoplasms Intervention:   Drug: Pembrolizumab 25 MG/1 ML Intravenous Solution [KEYTRUDA] Sponsor:   Henry Ford Health System Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conclusion: The addition of RT to CT resulted in longer OS in patients with limited stage head and neck DLBCL with extranodal involvement. PMID: 31793408 [PubMed - in process]
Source: Hematology - Category: Hematology Tags: Hematology Source Type: research
Opinion statementStandard-of-care treatment for the majority of patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) is either upfront surgery followed by adjuvant treatment as indicated by intraoperative or pathologic findings or concurrent chemoradiation reserving surgical salvage for non-responsive disease. An attempt at upfront complete resection should be pursued if feasible in patients with oral cavity or paranasal sinus primary tumors. Given multimodality treatment paradigms, patients with locoregionally advanced SCCHN should be managed in a multidisciplinary setting. Modern rad...
Source: Current Treatment Options in Oncology - Category: Cancer & Oncology Source Type: research
CONCLUSION: This combination demonstrated activity in HN, with fewer responses in SGC. Toxicities were higher than reported with pembrolizumab alone. PMID: 31796519 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
AbstractImmunotherapy is now widely established as a potent and effective treatment option across several types of cancer. However, there is increasing recognition that not all patients respond to immunotherapy, focusing attention on the immune contexture of the tumor microenvironment (TME), drivers of the immune response and mechanisms of tumor resistance to immunity. The development of novel immunotherapeutics and their use in combination with checkpoint inhibitors and other standard of care and novel treatment modalities is an area of particular attention across several tumor types, including melanoma, lung, ovarian, br...
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Pembrolizumab held advanced head and neck cancers in a group of patients at bay for around two years.
Source: BBC News | Health | UK Edition - Category: Consumer Health News Source Type: news
In my cancer immunology class, we discussed immunotherapies for various head and neck cancers. We had a surgical oncologist come in and talk about his work as well. What I'm curious about is, how will immunotherapies affect surgical treatment of H&N cancers? Will it render surgical intervention obsolete or will it help surgeons more easily resect the tumors?
Source: Student Doctor Network - Category: Universities & Medical Training Authors: Tags: Medical Students - MD Source Type: forums
Abstract BACKGROUND: Treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with programmed cell death protein 1 (PD-1) inhibitors has been associated with risk of developing immune-mediated adverse reactions (IMARs). OBJECTIVES: This review provides nurses with an overview of the safety of PD-1 inhibitors approved by the U.S. Food and Drug Administration for recurrent or metastatic SCCHN following platinum chemotherapy, as well as recommendations for assisting with the diagnosis and management of IMARs. METHODS: PubMed® searches were conducted to iden...
Source: Clinical Journal of Oncology Nursing - Category: Nursing Authors: Tags: Clin J Oncol Nurs Source Type: research
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Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
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