Abstract 546: Impact of therapeutic EGFR inhibition on immune checkpoint blockade in head and neck squamous cell carcinoma

2016 ◽  
Author(s):  
Laura M. Rogers ◽  
Madelyn M. Espinosa-Cotton ◽  
Andrean L. Simons ◽  
George J. Weiner
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Neck Squamous Cell Carcinoma ◽  
Egfr Inhibition

Immunotherapy of head and neck squamous cell carcinoma (HNSCC). Immune checkpoint blockade

2018 ◽  
Vol 72 (4) ◽  
pp. 1-5 ◽  
Author(s):  
Krzysztof Przybylski ◽  
Ewa Majchrzak ◽  
Liucija Weselik ◽  
Wojciech Golusiński
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Neck Squamous Cell Carcinoma

Leczenie chorych na raka płaskonabłonkowego głowy i szyi jest istotnym problemem. Obserwuje się wzrost zachorowalności na nowotwory złośliwe tego regionu. Chirurgia, radioterapia oraz chemioterapia często nie są wystarczającymi metodami leczenia. Dokładna analiza procesów zachodzących w mikrośrodowisku guza pozwoliła na wyodrębnienie trzech etapów składających się na reakcję organizmu człowieka na wrogie antygeny, jakimi są antygeny nowotworowe. Poznanie tych mechanizmów skutkowało wprowadzeniem nowego terminu immunoonkologia. Jest to dziedzina leczenia nowotworów skupiająca się na wykorzystaniu układu immunologicznego pacjenta w celu zwalczania choroby. Immunoterapia u chorych na raka przyniosła pozytywne efekty. Wykorzystanie inhibitorów immunologicznych punktów kontroli, jak przeciwciała monoklonalne przeciwko receptorowi CTLA – 4 oraz PD – 1 umożliwiło modulację funkcji limfocytów T w konsekwencji znosząc immunosupresję w mikrośrodowisku guza. Przeprowadzono badania kliniczne z zastosowaniem nivolumabu oraz ipilimumabu, które potwierdziły ich przydatność kliniczną. Zatwierdzenie przez FDA nivolumabu w leczeniu nawrotowego i przerzutowego raka płaskonabłonkowego głowy i szyi wydłużyło całkowity czas przeżycia chorych oraz czas przeżycia wolny od choroby. Dane statystyczne wskazują na przewagę immunoterapii nad innymi metodami leczenia w zaawansowanym stadium choroby nowotworowej. Celem pracy jest omówienie podstawowych zagadnień związanych z immunoterapią, w szczególności immunoterapią u chorych na raka płaskonabłonkowego głowy i szyi.

scholarly journals Genomic and Molecular Profiling of Human Papillomavirus Associated Head and Neck Squamous Cell Carcinoma Treated with Immune Checkpoint Blockade Compared to Survival Outcomes

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6309
Author(s):  
Hira Shaikh ◽  
Julie E. McGrath ◽  
Brittany Hughes ◽  
Joanne Xiu ◽  
Pavel Brodskiy ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Neck Squamous Cell Carcinoma ◽  
Common Mutation

Recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients overall have a poor prognosis. However, human papillomavirus (HPV)-associated R/M oropharyngeal squamous cell carcinoma (OPSCC) is associated with a better prognosis compared to HPV−negative disease. Immune checkpoint blockade (ICB) is the standard of care for R/M HNSCC. However, whether HPV and its surrogate marker, p16, portend an improved response to ICB remains controversial. We queried the Caris Life Sciences CODEai database for p16+ and p16− HNSCC patients using p16 as a surrogate for HPV. A total of 2905 HNSCC (OPSCC, n = 948) cases were identified. Of those tested for both HPV directly and p16, 32% (251/791) were p16+ and 28% (91/326) were HPV+. The most common mutation in the OPSCC cohort was TP53 (33%), followed by PIK3CA (17%) and KMT2D (10.6%). TP53 mutations were more common in p16− (49%) versus the p16+ group (10%, p < 0.0005). Real-world overall survival (rwOS) was longer in p16+ compared to p16− OPSCC patients, 33.3 vs. 19.1 months (HR = 0.597, p = 0.001), as well as non-oropharyngeal (non-OP) HNSCC patients (34 vs. 17 months, HR 0.551, p = 0.0001). There was no difference in the time on treatment (TOT) (4.2 vs. 2.8 months, HR 0.796, p = 0.221) in ICB-treated p16+ vs. p16− OPSCC groups. However, p16+ non-OP HNSCC patients treated with ICB had higher TOT compared to the p16− group (4.3 vs. 3.3 months, HR 0.632, p = 0.016), suggesting that p16 may be used as a prognostic biomarker in non-OP HNSCC, and further investigation through prospective clinical trials is warranted.

Chemotherapy after immune checkpoint blockade in patients with recurrent, metastatic squamous cell carcinoma of the head and neck

Oral Oncology ◽  
2020 ◽  
Vol 105 ◽  
pp. 104676 ◽  
Author(s):  
Alec J. Kacew ◽  
Ethan J. Harris ◽  
Jochen H. Lorch ◽  
Jonathan D. Schoenfeld ◽  
Danielle N. Margalit ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Metastatic Squamous Cell Carcinoma

scholarly journals The Current Landscape of Immune Checkpoint Blockade in Metastatic Lung Squamous Cell Carcinoma

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1392
Author(s):  
Hong Yuan ◽  
Jing Liu ◽  
Jun Zhang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Unmet Need ◽  
Lung Squamous Cell Carcinoma ◽  
Standard Of Care ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Programmed Death

In addition to surgery, chemotherapy, radiotherapy, and targeted therapy, immunotherapy has emerged as a standard pillar of cancer treatment. Immune checkpoint inhibitors (ICIs) such as targeting programmed death-1/programmed death ligand 1 (PD-1/PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) have been integrated into standard-of-care regimens for patients with advanced lung squamous cell carcinoma (LUSC), who were previously limited by the lack of treatment options. Atezolizumab, durvalumab, nivolumab, and pembrolizumab are all currently used as part of standard-of-care treatment for different stages of lung cancer. Recent successes and failures of immune checkpoint blockade-based combination therapies have provided significant insights into implementing combination strategies in LUSC. Therefore, there is an urgent need to correctly select patients who are more likely to respond to immunotherapy and understand the mechanisms of primary or acquired resistance. In this review, we aim at summarizing the emerging clinical data on the promise and challenge of ICIs, discussing the unmet need of potential biomarkers for predicting response or resistance to immunotherapy, and providing an overview of the current immune landscape and future directions in advanced LUSC.

scholarly journals Clinical Outcomes of Cetuximab and Paclitaxel after Progression on Immune Checkpoint Inhibitors in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Medicina ◽  
2021 ◽  
Vol 57 (11) ◽  
pp. 1151
Author(s):  
Shinsuke Suzuki ◽  
Satoshi Toyoma ◽  
Yohei Kawasaki ◽  
Koh Koizumi ◽  
Nobuko Iikawa ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Neck Squamous Cell Carcinoma ◽  
Grade 3

Background and Objectives: In recent years, the effectiveness of chemotherapy after immune checkpoint inhibitor administration has attracted attention in various cancers, including head and neck cancers. However, individual assessments of the administered chemotherapy regimens are insufficient. This study aimed to evaluate the efficacy and safety of chemotherapy after immune checkpoint inhibitor administration in recurrent metastatic head and neck cancer by focusing on a single regimen. Materials and Methods: We retrospectively reviewed clinical and radiological data from the medical records of 18 patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who received systemic chemotherapy with weekly cetuximab and paclitaxel (Cmab + PTX) after progression following immune checkpoint inhibitor (ICI) therapy. The objective response rate (ORR) and disease control rate (DCR) were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Adverse events (AEs) were recorded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Results: In all patients, the ORR, DCR, median PFS, and median OS were 44.4%, 72.2%, 3.8 months, and 9.6 months, respectively. Regarding AEs, three patients developed grade 3 neutropenia. Grade 3 anemia, paronychia, asthenia, and peripheral neuropathy were observed in one patient each. There were no treatment-related deaths. Conclusions: Cmab + PTX was shown to maintain high efficacy and acceptable safety for R/M HNSCC that progressed after ICI therapy. Further research is needed to establish optimal treatment sequences and drug combinations for recurrent R/M HNSCC.

scholarly journals Gene Model Related to m6A Predicts the Prognostic Effect of Immune Infiltration on Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yaping Deng ◽  
Kehua Li ◽  
Fengwu Tan ◽  
Hanbo Liu
Keyword(s):  
Immune Response ◽  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Risk Score ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Neck Squamous Cell Carcinoma ◽  
Immune Microenvironment

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive solid tumor. Because most studies have focused on the intrinsic carcinogenic pathways of tumors, we focused on the relationship between N6-methyladenosine (m6A) and the prognosis of HNSCC in the tumor immune microenvironment. We downloaded RNA-seq data from the TCGA dataset and used univariate Cox regression to screen m6A-related lncRNAs. The expression value of LASSO-screened genes was the sum of LASSO regression coefficients. We then evaluated relationships between the risk score and cellular components or cellular immune response. Differences in immune response under various algorithms were visualized with heat maps. The GSVA package in R was used to analyze GO, BP, KEGG, and hallmark gene sets of immune checkpoint clusters and immune checkpoint scores. The GSEA analysis was performed with the cluster profile package, yielding 21 m6A genes. Related lncRNAs were screened with Pearson’s correlations, and the resulting 442 lncRNAs were screened using single-factor analysis. Eight lncRNAs closely related to prognosis were identified through survival random forest. Survival analysis showed that patients with a high risk score had a poor prognosis. Low- and high-risk-score groups differed significantly in m6A gene expression. Prognostic scores from different algorithms were significantly correlated with B cells, T cells, and memory cells in the immune microenvironment. Expression of immune checkpoints and signal pathways differed significantly across risk-score groups, suggesting that m6A could mediate lncRNA-induced immune system dysfunction and affect HNSCC development. A comprehensive study of tumor-cell immune characteristics should provide more insight into the complex immune microenvironment, thus contributing to the development of new immunotherapeutic agents.

Sign in / Sign up

Export Citation Format

Share Document