scholarly journals Overcoming Resistance to Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinomas

2021 ◽  
Vol 11 ◽  
Author(s):  
Lucas V. dos Santos ◽  
Carina M. Abrahão ◽  
William N. William
Keyword(s):  
Head And Neck ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
De Novo ◽  
Checkpoint Inhibitors ◽  
Acquired Resistance ◽  
Clinical Work ◽  
Squamous Cell Carcinomas ◽  
Clinical Activity

Preclinical data suggest that head and neck squamous cell carcinomas (HNSCC) may evade immune surveillance and induce immunosuppression. One mechanism of immune evasion involves the expression of programmed death ligand-1 (PD-L1) in tumor and immune cells, which is, to date, the only biomarker routinely used in clinical practice to select patients with advanced HNSCCs more likely to benefit from anti-PD-1 therapy. Nonetheless, PD-L1 expression alone incompletely captures the degree of sensitivity of HNSCCs to PD-1 inhibitors. Most patients exposed to anti-PD-1 antibodies do not respond to therapy, suggesting the existence of mechanisms of de novo resistance to immunotherapy. Furthermore, patients that initially respond to PD-1 inhibitors will eventually develop acquired resistance to immunotherapy through mechanisms that have not yet been completely elucidated. In this article, we will provide an overview of the immune landscape of HNSCCs. We will briefly describe the clinical activity of inhibitors of the PD-1/PD-L1 axis in this disease, as well as biomarkers of benefit from these agents that have been identified so far. We will review pre-clinical and clinical work in cancers in general, and in HNSCCs specifically, that have characterized the mechanisms of de novo and acquired resistance to immunotherapy. Lastly, we will provide insights into novel strategies under investigation to overcome resistance to immune checkpoint inhibitors.

scholarly journals Neoadjuvant immunotherapy in resectable head and neck cancer: oral cavity carcinoma as a potential research model

2021 ◽  
Vol 13 ◽  
pp. 175883592098406
Author(s):  
Vanesa Gutiérrez Calderón ◽  
Alexandra Cantero González ◽  
Laura Gálvez Carvajal ◽  
Yolanda Aguilar Lizarralde ◽  
Antonio Rueda Domínguez
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Surgical Resection ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Research Model

Squamous cell carcinoma of oral cavity (OCSCC) accounts for approximately 25% of cases of head and neck squamous cell carcinoma (HNSCC). Tobacco and alcohol consumption are the main risk factors for both cancers. Surgical resection, combined with adjuvant radiotherapy or radiochemotherapy in patients with high risk of relapse, is the key element in management in the initial stages. However, despite the availability of aggressive multidisciplinary treatments, advanced resectable OCSCC carries poor prognosis; only half of the patients are disease-free 5 years after the surgery. Immunotherapy based on the use of immune checkpoint inhibitors has been proven to be effective in a wide variety of tumours, including recurrent and metastatic HNSCC. These positive results resulted in investigations into its effectiveness in earlier stages of the disease with OCSCC emerging as an interesting research model because of the accessible location of the tumours. This article reviews the potential advantages of emerging immunotherapeutic agents [mainly monoclonal antibodies against programmed cell death-1 ( PD-1) immune checkpoint inhibitors] as neoadjuvant treatment for OCSCC at locoregional stages as well as the ongoing clinical trials, challenges in evaluating tumour response, and possible predictive biomarkers of response with highlights regarding the role of oral microbiota as modulators of immune response. The efficacy and safety of anti- PD-1 drugs in these patients have been proven in preliminary trials. If there is a decrease in the relapse rate and an improvement in the overall survival after surgical resection in ongoing trials, preoperative immunotherapy may be established as a treatment option for patients with early stages of the disease.

scholarly journals Exploration of Feasible Immune Biomarkers for Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinoma Treatment in Real World Clinical Practice

2020 ◽  
Vol 21 (20) ◽  
pp. 7621
Author(s):  
Hui-Ching Wang ◽  
Tsung-Jang Yeh ◽  
Leong-Perng Chan ◽  
Chin-Mu Hsu ◽  
Shih-Feng Cho
Keyword(s):  
Squamous Cell Carcinoma ◽  
Clinical Practice ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Clinical Outcomes ◽  
Squamous Cell ◽  
Real World ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors

Recurrent locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC) is associated with dismal prognosis because of its highly invasive behavior and resistance to conventional intensive chemotherapy. The combination of targeted therapy and conventional chemotherapy has significantly improved clinical outcomes. In recent years, the development of immunotherapies, such as immune checkpoint inhibitors (ICIs), has further increased treatment responses and prolonged survival. However, the limited response rate, risk of immunotherapy-related adverse effects and high cost of immunotherapy make the identification of predictive markers to optimize treatment efficacy a critical issue. Biomarkers are biological molecules that have been widely utilized to predict treatment response to certain treatments and clinical outcomes or to detect disease. An ideal biomarker should exhibit good predictive ability, which can guide healthcare professionals to achieve optimal treatment goals and bring clinical benefit to patients. In this review, we summarized the results of recent and important studies focused on HNSCC ICI immunotherapy and discussed potential biomarkers including their strengths and limitations, aiming to gain more insight into HNSCC immunotherapy in real world clinical practice.

Efficacy and safety of immune checkpoint inhibitors in elderly patients (≥70 years) with squamous cell carcinoma of the head and neck.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6035-6035
Author(s):  
Caroline Even ◽  
Nicolas Martin ◽  
Edith Borcoman ◽  
Anne Auperin ◽  
Nouritza Torossian ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Efficacy And Safety ◽  
Eligibility Criteria ◽  
Grade 3

6035 Background: Recent meta-analysis showed that immune checkpoint inhibitors (ICI) have comparable activity in younger vs older patients (pts) (≥65 years (y)). However little is known about efficacy and safety of ICI in elderly pts with relapsed/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). The aim of this study is to compare efficacy and grade ≥3 immune-related adverse events (irAEs) of ICI in pts ≥70 y with R/M SCCHN to younger pts. Methods: A retrospective study was conducted at 4 French hospitals. Eligibility criteria were pts treated with ICI for R/M SCCHN between September 2014 and December 2018. Clinical and radiological data and outcome were collected from review of medical records. Results: Two hundred twenty six pts were enrolled including 67 pts ≥ 70 y. Median age of elderly pts was 75y (range 70-87). Elderly pts received ICI as first-line treatment in 21% of pts vs 17% in younger pts. In elderly pts, 9% had ECOG of 0, 72% had ECOG of 1 and 15% had ECOG of 2 at ICI initiation vs 34%, 62% and 4% respectively in younger pts (p = 0.0006). In elderly pts, 22% had only loco-regional relapse at ICI initiation, 30% only distant recurrence and 49% had both vs 42%, 32% and 26% respectively (p = 0.0014). Elderly pts received ICI as monotherapy in 73% of pts vs 52% (p = 0.0027). The ORR in elderly pts was 23% vs 13% in younger pts (p = 0.071). After a median follow-up of 16.8 months (m) (range 10.7-23.7), median OS was 9.7m in elderly pts vs 8.7m in younger pts (p = 0.87). Median PFS was 2.7 m in elderly pts vs 1.9 m (p = 0.2). After adjustment for ECOG, type of evolution, number of ICI drugs, time between initial diagnosis and ICI start and number of previous lines, age ≥70 years was significantly associated with a better PFS (HR = 0.66 (95%CI = 0.47;0.93), p = 0.02) but was not significantly associated with OS (HR = 0.91 (95%CI = 0.61;1.34), p = 0.62). Grade ≥3 irAEs occurred in 15% of elderly pts vs 8% of younger pts (p = 0.13). Patients with grade ≥3 irAEs had a significantly higher ORR than pts without Grade ≥3 irAEs (36% vs 14%, p = 0.007). Conclusions: Elderly pts treated with ICI had significantly higher PFS but not OS after adjustment. Grade ≥3 irAEs were associated with significantly higher ORR to ICI in the whole population.

scholarly journals Oropharyngeal Squamous Cell Carcinoma Treatment in the Era of Immune Checkpoint Inhibitors

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1234
Author(s):  
Peter L. Stern ◽  
Tina Dalianis
Keyword(s):  
Squamous Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Effective Means ◽  
Immune Surveillance ◽  
Standard Of Care ◽  
Tumour Microenvironment ◽  
Squamous Cell Carcinomas

While head and neck squamous cell carcinomas (HNSCC) are marginally decreasing due to the reduction in exposure to the major risk factors, tobacco and alcohol, the incidence of high-risk human papillomavirus (HPV)-positive oropharynx squamous cell carcinomas (OPSCC), especially those in the tonsil and base of tongue subsites, are increasing. Patients with the latter are younger, display a longer overall survival, and show a lower recurrence rate after standard-of-care treatment than those with HPV-negative OPSCC. This may reflect an important role for immune surveillance and control during the natural history of the virally driven tumour development. Immune deviation through acquisition of immune-suppressive factors in the tumour microenvironment (TME) is discussed in relation to treatment response. Understanding how the different immune factors are integrated in the TME battleground offers opportunities for identifying prognostic biomarkers as well as novel therapeutic strategies. OPSCC generally receive surgery or radiotherapy for early-stage tumour treatment, but many patients present with locoregionally advanced disease requiring multimodality therapies which can involve considerable complications. This review focuses on the utilization of newly emerged immune checkpoint inhibitors (PD-1/PD-L1 pathway) for treatment of HNSCC, in particular HPV-positive OPSCC, since they could be less toxic and more efficacious. PD-1/PD-L1 expression in the TME has been extensively investigated as a biomarker of patient response but is yet to provide a really effective means for stratification of treatment. Extensive testing of combinations of therapeutic approaches by types and sequencing will fuel the next evolution of treatment for OPSCC.

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