Immune Checkpoint Inhibition in Head and Neck Cancer

Förster, Martin; Devlin, Michael-John

doi:10.3389/fonc.2018.00310

Cited by 102 publications

(90 citation statements)

References 77 publications

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“…Consequently, a low ORR poses a risk of early progression and mortality. Several combination therapies were proposed to improve the efficacy of ICI monotherapy, including ICI plus chemotherapy and dual ICI therapy (http://ClinicalTrials.gov, NCT02358031; NCT02823574; NCT02741570; NCT02551159) . Novel agents and treatment strategies are required to improve immunotherapy efficacy in HNSCC treatment.…”

Section: Discussionmentioning

confidence: 99%

Novel immune‐modulating drugs for advanced head and neck cancer

2019

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Background Recently, two anti‐PD‐1 immune checkpoint inhibitors, pembrolizumab and nivolumab, have been approved by the US Food and Drug Administration for patients who fail on platinum‐based chemotherapy. However, overall response and progression‐free survival are still limited, and multiple novel agents are under development to fulfill this unmet clinical need. Methods Publications between 1992 and 2019 regarding the immunological/biological mechanisms and early phase clinical trial outcomes of immunomodulatory agents for head and neck cancer were described in this review article. Results Eleven immunomodulatory agents for advanced head and neck, including small molecules, antibodies, and therapeutic vaccines were described. Treatment responses were noted in nearly all 11 agents, as monotherapy or combination therapy. Conclusions Potentials of the novel immunomodulatory agents to improve treatment efficacy of head and neck cancer and to maintain tolerable safety profile have been disclosed.

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Section: Discussionmentioning

confidence: 99%

Novel immune‐modulating drugs for advanced head and neck cancer

2019

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“…Recently, patients with advanced H&N cancer were treated successfully with immune checkpoint blockade antibodies (pembrolizumab or nivolumab) as a subsequent therapeutic option . However, the rate of recurrence of localized squamous cell carcinoma of the H&N (SCCHN) is approximately 10% to 20%, and the incidence of locally advanced SCCHN is approximately 50% . Patients with recurrent or metastatic SCCHN have a poor prognosis, and the median overall survival is <1 year .…”

Section: Introductionmentioning

confidence: 99%

“…11,12 However, the rate of recurrence of localized squamous cell carcinoma of the H&N (SCCHN) is approximately 10% to 20%, 13 and the incidence of locally advanced SCCHN is approximately 50%. 14 Patients with recurrent or metastatic SCCHN have a poor prognosis, and the median overall survival is <1 year. 15 Thus, there is a need for new therapies to effectively treat this devastating disease.…”

Section: Introductionmentioning

confidence: 99%

A randomized, phase 1, placebo‐controlled trial of APG‐157 in oral cancer demonstrates systemic absorption and an inhibitory effect on cytokines and tumor‐associated microbes

Basak

Bera

Yoon

et al. 2020

Cancer

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Background Although curcumin's effect on head and neck cancer has been studied in vitro and in vivo, to the authors' knowledge its efficacy is limited by poor systemic absorption from oral administration. APG‐157 is a botanical drug containing multiple polyphenols, including curcumin, developed under the US Food and Drug Administration's Botanical Drug Development, that delivers the active components to oromucosal tissues near the tumor target. Methods A double‐blind, randomized, placebo‐controlled, phase 1 clinical trial was conducted with APG‐157 in 13 normal subjects and 12 patients with oral cancer. Two doses, 100 mg or 200 mg, were delivered transorally every hour for 3 hours. Blood and saliva were collected before and 1 hour, 2 hours, 3 hours, and 24 hours after treatment. Electrocardiograms and blood tests did not demonstrate any toxicity. Results Treatment with APG‐157 resulted in circulating concentrations of curcumin and analogs peaking at 3 hours with reduced IL‐1β, IL‐6, and IL‐8 concentrations in the salivary supernatant fluid of patients with cancer. Salivary microbial flora analysis showed a reduction in Bacteroidetes species in cancer subjects. RNA and immunofluorescence analyses of tumor tissues of a subject demonstrated increased expression of genes associated with differentiation and T‐cell recruitment to the tumor microenvironment. Conclusions The results of the current study suggested that APG‐157 could serve as a therapeutic drug in combination with immunotherapy. Lay Summary Curcumin has been shown to suppress tumor cells because of its antioxidant and anti‐inflammatory properties. However, its effectiveness has been limited by poor absorption when delivered orally. Subjects with oral cancer were given oral APG‐157, a botanical drug containing multiple polyphenols, including curcumin. Curcumin was found in the blood and in tumor tissues. Inflammatory markers and Bacteroides species were found to be decreased in the saliva, and immune T cells were increased in the tumor tissue. APG‐157 is absorbed well, reduces inflammation, and attracts T cells to the tumor, suggesting its potential use in combination with immunotherapy drugs.

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“…As understanding of the interactions between cancer cells and tumor microenvironment improves, there is gathering evidences on the role of immunotherapy agents in the management of OSCC . Inhibitory interaction between programmed cell death protein 1 (PD‐1) and its ligand programmed cell death 1 ligand 1 (PD‐L1), which are the most typical immune checkpoint inhibitors, has exhibited durable improvements in patient clinical outcomes in advanced/metastatic OSCC . There are also numerous ongoing clinical trials exploring the role of checkpoint inhibitory agents in the way of single agents or in combination, administered with traditional modalities such as chemotherapy and radiotherapy, as well as alongside other novel immune modulators .…”

Section: Introductionmentioning

confidence: 99%

“…5 Inhibitory interaction between programmed cell death protein 1 (PD-1) and its ligand programmed cell death 1 ligand 1 (PD-L1), which are the most typical immune checkpoint inhibitors, has exhibited durable improvements in patient clinical outcomes in advanced/ metastatic OSCC. 6 There are also numerous ongoing clinical trials exploring the role of checkpoint inhibitory agents in the way of single agents or in combination, administered with traditional modalities such as chemotherapy and radiotherapy, as well as alongside other novel immune modulators. 7 As researches complete and more results become available, the role of checkpoint inhibitors will lead to an explosion in interest in the immune system and how to harness it to fight OSCC, with more promising biomarkers being picked out and resulting in individual treatment aiming to further improve patient outcomes.…”

Section: Introductionmentioning

confidence: 99%

Altered expression of TIM‐3, LAG‐3, IDO, PD‐L1, and CTLA‐4 during nimotuzumab therapy correlates with responses and prognosis of oral squamous cell carcinoma patients

Wang

Mao

Zhang

et al. 2019

J Oral Pathology Medicine

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Background Since the inhibitory immune checkpoint receptors have been described to benefit the OSCC patients clinically, it is unknown that whether their expression in tumor immune microenvironment (TME) can determine the clinical outcome in response to nimotuzumab therapy. Methods We examined the expression patterns of immune checkpoint receptors (including TIM‐3, LAG‐3, PD‐L1, and CTLA‐4) and an immunoregulatory enzyme called IDO in 36 OSCC patients during nimotuzumab therapy by immunohistochemistry. Then, we divided the recruited patients into clinical responders and non‐responders according to computed tomography (CT) scan and analyzed the relationship between the immunological parameters and clinical outcome. Results We observed that nimotuzumab therapy significantly increased the expression of TIM‐3, LAG‐3, IDO, PD‐L1, and CTLA‐4 in the TME, and the expression of LAG‐3 and PD‐L1 before nimotuzumab therapy was inversely correlated with the overall survival. In clinical non‐responders, we found the expression of TIM‐3, LAG‐3, IDO, PD‐L1, and CTLA‐4 was significantly increased during nimotuzumab therapy, and the expression of TIM‐3, LAG‐3, IDO, PD‐L1, and CTLA‐4 before nimotuzumab therapy was negatively correlated with the overall survival. However, in clinical responders, neither of those showed significant. Conclusions It suggests that these immune checkpoint receptors and IDO could be considered as biomarkers to reflect immune status in the tumor microenvironment during nimotuzumab therapy. Blockade of these immune checkpoint receptors might enhance nimotuzumab‐based cancer immunotherapy, thus potentially improving clinical outcomes of OSCC patients.

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Immune Checkpoint Inhibition in Head and Neck Cancer

Cited by 102 publications

References 77 publications

Novel immune‐modulating drugs for advanced head and neck cancer

Novel immune‐modulating drugs for advanced head and neck cancer

A randomized, phase 1, placebo‐controlled trial of APG‐157 in oral cancer demonstrates systemic absorption and an inhibitory effect on cytokines and tumor‐associated microbes

Altered expression of TIM‐3, LAG‐3, IDO, PD‐L1, and CTLA‐4 during nimotuzumab therapy correlates with responses and prognosis of oral squamous cell carcinoma patients

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