Immunotherapy in Patients with Recurrent and Metastatic Squamous Cell Carcinoma of the Head and Neck

2019 ◽  
Vol 19 (3) ◽  
pp. 290-303 ◽  
Author(s):  
Izabela Łasińska ◽  
Tomasz Kolenda ◽  
Anna Teresiak ◽  
Katarzyna M. Lamperska ◽  
Łukasz Galus ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Head And Neck Cancer ◽  
Cancer Treatment ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Neck Cancer ◽  
Squamous Cell ◽  
Locally Advanced ◽  
New Drugs ◽  
Radical Treatment

Background:Head and neck squamous cell carcinoma (HNSCC) is the most common malignant cancer occurring in the head and neck area, approximately 90% of the cases. Even in the cases of primary radical treatment (surgical, concomitant chemoradiotherapy or radiotherapy alone), subsequent local recurrence or distant metastases are often observed. In patients with recurrent disease who are unable to receive radical treatment, the results of palliative chemotherapy are not satisfactory. In this review, we summarized the standard treatment options, current development of new drugs and future perspectives in the treatment of patients with recurrent locally advanced and/or metastatic HNSCC.Methods:PubMed databases with words ‘head and neck cancer treatment’, ‘immunotherapy in head and neck cancer treatment’ were searched and yielded 186512 and 2249 papers respectively. We selected the most cited articles and reports presenting new immunotherapy agents and drug combinations in HNSCC.Results:Recently, two new agents been approved in the treatment of recurrent locally advanced and/or metastatic HNSCC. These are immune-checkpoint inhibitors targeting PD1 (nivolumab and pembrolizumab) which are the most active drugs in the second line treatment of advanced HNSCC. Still, the first line ‘golden standard’ is the chemotherapy regimen (cisplatin, 5-fluorouracyl) combined with cetuximab. Many phase 3 studies are currently ongoing, evaluating the efficacy of combinational treatment-anti-CTLA4 with anti-PD1 or anti-PDL1. Very encouraging results have been shown in early phase studies evaluating the combination of immunecheckpoint inhibitors with tumor microenvironment immunosuppressive inhibitors.Conclusion:Despite the huge progress in the systemic treatment of patients with recurrent locally advanced and/or metastatic HNSCC, the disease at this stage remains incurable. Undoubtedly, further research in the field of biomarkers for effective immunotherapy is needed in order to select a group of patients whose will benefit from this therapy, as the treatment is still ineffective in most patients.

Optimal cumulative cisplatin dose for radio-sensitization in locally advanced head and neck cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18553-e18553
Author(s):  
Atanu Bhattacharjee ◽  
Vanita Noronha ◽  
Vijay Maruti Patil ◽  
Anuja Abhayankar ◽  
Amit Joshi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Head And Neck Cancer ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Neck Cancer ◽  
Squamous Cell ◽  
Cumulative Dose ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Free Survival

e18553 Background: Evidence to choose the optimum chemotherapy between weekly and 3 weekly cisplatin for prolonging the duration of progression free survival in head and neck squamous cell carcinoma (HNSCC) is equivocal. This urged us to look into the cumulative dose of chemotherapy rather than the frequency of administration i.e. weekly or 3 weekly. The aim of this study was to determine the optimal cumulative dose of cisplatin to improve the progression-free survival (PFS). Methods: Between January 2011 and January 2018, a total of 836 consecutive patients with histologically proven primary squamous cell carcinoma of the oral cavity, larynx, hypopharynx, and oropharynx were included. The effect of the cumulative dose on progression-free survival was studied to obtain the optimal cumulative dose of cisplatin. Results: A total of 11 cohorts were generated to represent the cumulative doses. The cumulative doses were measured at 30, 60, 90,120,150,180,200,210,240 and 300 mg/m2 respectively. The maximum duration of progression-free survival (PFS) was considered to define the best effective cumulative dose. Conclusions: This study confirms that a cumulative cisplatin dose of ~ 210 mg/m2 is optimum for increasing PFS in patients with head and neck cancer. Therefore, doses with weekly 30 mg/m2 for seven cycles or 3-weekly 70 mg/m2 for 3 cycles could be equally effective to prolong the PFS. Clinical trial information: CTRI/2012/10/003062, CTRI/2014/09/004980.

scholarly journals Radiotherapy and Immunotherapy for Head and Neck Cancer: Current Evidence and Challenges

2021 ◽  
Vol 10 ◽  
Author(s):  
Jack M. Qian ◽  
Jonathan D. Schoenfeld
Keyword(s):  
Squamous Cell Carcinoma ◽  
Head And Neck Cancer ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Neck Cancer ◽  
Squamous Cell ◽  
Clinical Evidence ◽  
Locally Advanced ◽  
Neck Squamous Cell Carcinoma ◽  
Current Evidence

Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment over the past decade. However, although the immune landscape suggests a strong rationale for the use of these agents in patients with head and neck squamous cell carcinoma, the available clinical evidence indicates that most patients currently do not respond to ICI monotherapy. Radiotherapy is a primary treatment modality for many patients with locally advanced head and neck cancer. While ionizing radiation traditionally has been thought to act in a purely cytotoxic fashion, a growing body of preclinical studies have demonstrated additional profound immunomodulatory effects. Consequently, there has been a surge of interest in the potential synergy between radiotherapy and immunotherapy, both the potential for radiotherapy to augment the systemic anti-tumor immune response and the potential for immunotherapy to improve in-field tumor response to radiation. In this review, we summarize the current preclinical and clinical evidence for radioimmunotherapy, with a particular focus on studies directly relevant to head and neck squamous cell carcinoma, as well as existing challenges and future directions for this emerging field.

Follow-up strategies in head and neck cancer other than upper aerodigestive tract squamous cell carcinoma

2012 ◽  
Vol 270 (7) ◽  
pp. 1981-1989 ◽  
Author(s):  
Antoine Digonnet ◽  
Marc Hamoir ◽  
Guy Andry ◽  
Vincent Vander Poorten ◽  
Missak Haigentz ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Head And Neck Cancer ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Neck Cancer ◽  
Squamous Cell ◽  
Aerodigestive Tract ◽  
Upper Aerodigestive Tract

Squamous cell carcinoma DNA detection using ultrabright SERS nanorattles and magnetic beads for head and neck cancer molecular diagnostics

2017 ◽  
Vol 9 (37) ◽  
pp. 5550-5556 ◽  
Author(s):  
P. Vohra ◽  
H. T. Ngo ◽  
W. T. Lee ◽  
T. Vo-Dinh
Keyword(s):  
Squamous Cell Carcinoma ◽  
Head And Neck Cancer ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Molecular Diagnostics ◽  
Neck Cancer ◽  
Squamous Cell ◽  
Magnetic Beads ◽  
Low Cost ◽  
Diagnostic Technologies

A rise in head and neck cancers in low and middle countries over recent years has prompted the need for low-cost, resource-efficient diagnostic technologies.

scholarly journals 903 Human cancer-associated fibroblast subsets can predict immune checkpoint response in head and neck cancer patients

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A947-A947
Author(s):  
Diana Graves ◽  
Aleksandar Obradovic ◽  
Michael Korrer ◽  
Yu Wang ◽  
Sohini Roy ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
T Cells ◽  
Head And Neck Cancer ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Single Cell ◽  
Rna Sequencing ◽  
Neck Cancer ◽  
Squamous Cell ◽  
Single Cell Rna Sequencing

BackgroundUse of anti-PD-1 immune checkpoint inhibitors (ICI) is currently the first line therapy for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but critical work remains in identifying factors guiding resistance mechanisms.1 2 While recent studies have specifically implicated cancer-associated fibroblasts (CAFs) as potential mediators of immunotherapy response, the immunoregulatory role of CAFs in head and neck cancer has not been thoroughly explored.3–5MethodsTo determine if there are changes in cell populations associated with anti-PD-1 therapy in head and neck cancer patients, we performed high dimensional single-cell RNA sequencing (scRNA-SEQ) from a neoadjuvant trial of 50 advanced-stage head and neck squamous cell carcinoma (HNSCC) patients that were treated with the anti-PD-1 therapy, nivolumab, for the duration of one month. Tumor specimens were analyzed pre- and post-treatment with single-cell RNA sequencing performed on 4 patients as well as bulk RNA sequencing on 40 patients. Matched scRNA-SEQ data was analyzed using the Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe) and Virtual Inference of Protein-activity by Enriched Regulon (VIPER) bioinformatic analysis platform to determine TME cells that correlated with response and resistance to nivolumab.6 For CAF functional studies, surgical tumor specimens were processed and enriched for CAF subtypes, and these were co-cultured with T cells from peripheral blood and tumor infiltrating lymphocytes.ResultsWe identified 14 distinct cell types present in HNSCC patients. Of these 14 cell types, the fibroblast subtype showed significant changes in abundance following nivolumab treatment. We identified 5 distinct clusters of cancer-associated fibroblast subsets (HNCAF-0, 1, 2, 3, and 4) of which, two clusters, HNCAF-0 and HNCAF-3 were predictive of patient response to anti-PD-1 therapy. To determine the significance of these CAF subsets’ function, we isolated HNCAF-0/3 cells from primary HNSCC tumor specimens and co-cultured with primary human T cells. Analysis by flow cytometry showed that HNCAF-0/3 reduced TGFβ-dependent PD-1+TIM-3+ exhaustion of T cells and increased CD103+NKG2A+ resident memory phenotype and cytotoxicity to enhance overall function.ConclusionsTo our knowledge, we are the first to characterize CAF heterogeneity within the head and neck TME and show direct immunostimulatory activity of CAFs. Our findings demonstrate the functional importance of CAF subsets in modulating the immunoregulatory milieu of the human HNSCC, and we have identified clinically actionable CAF subtypes that can be used as a biomarker of response and resistance in future clinical trials.Trial RegistrationNCT03238365ReferencesFerris RL, Blumenschein Jr G, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 2016;375:1856–1867.Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP, Heath K, McClanahan T, Lunceford J, Gause C, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol 2016;17:956–965.Dominguez CX, Muller S, Keerthivasan S, Koeppen H, Hung J, Gierke S, Breart B, Foreman O, Bainbridge TW, Castiglioni A, et al. Single-cell RNA sequencing reveals stromal evolution into LRRC15(+) myofibroblasts as a determinant of patient response to cancer immunotherapy. Cancer Discov 2020;10:232–253.Feig C, Jones JO, Kraman M, Wells RJ, Deonarine A, Chan DS, Connell CM, Roberts EW, Zhao Q, Caballero OL, et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci U S A 2013;110:20212–20217.Kieffer Y, Hocine HR, Gentric G, Pelon F, Bernard C, Bourachot B, Lameiras S, Albergante L, Bonneau C, Guyard A, et al. Single-cell analysis reveals fibroblast clusters linked to immunotherapy resistance in cancer. Cancer Discov 2020;10:1330–1351.Obradovic A, Chowdhury N, Haake SM, Ager C, Wang V, Vlahos L, Guo XV, Aggen DH, Rathmell WK, Jonasch E, et al. Single-cell protein activity analysis identifies recurrence-associated renal tumor macrophages. Cell 2021;184:2988–3005.Ethics ApprovalPatients provided informed consent for this work. All experimental procedures were approved by the Institutional Review Board of Vanderbilt University Medical Center (IRB: 171883).

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