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Cancers
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The Role of Immunotherapy in Squamous Cell Carcinoma
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The Role of Immunotherapy in Squamous Cell Carcinoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 10095

Special Issue Editor

Dr. Markus Heppt

E-Mail Website
Guest Editor
Department of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
Interests: cutaneous neoplasms; non-melanoma skin cancer; keratinocyte cancer; melanoma; ocular melanoma; immunotherapy

Special Issue Information

Dear Colleagues,

The field of oncology is rapidly evolving. For patients with recurrent/metastatic squamous cell carcinomas, the use of immunotherapy alone or in combination with different cytotoxic agents has shown improvements in both disease-free and overall survival.  Despite the promise and the clinical potential of immunotherapy, a large group of patients will progress within the first 2 years of treatment. Additionally, a segment of patients will experience rapid progression and poor outcome following treatment with immunotherapy. This highlights the need for reliable tools to identify potential candidates for treatment with immunotherapy.

In the realm of immunotherapy combinations, novel approaches are being tested such as programmed cell death 1 inhibitors and vaccines for HPV+ tumors, novel checkpoint inhibitor combinations, cellular therapies, and metronomic chemotherapy, among others. Last but not least, the use of novel therapies after progression on immune check point inhibitors is also of interest.

This Special Issue will highlight the current state of the art in the treatment of squamous cell carcinomas with immunotherapy and potential therapies available for treatment after progression on immunotherapy. This Issue will also highlight the role of predictive markers for the better selection of patients that will benefit from an initial treatment with immunotherapy. Lastly, this Issue will highlight the emerging role of novel immunotherapy targets and newer combination therapies for the management of this patient population.

We look forward to receiving your contributions.

Dr. Markus Heppt
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • squamous cell carcinoma
  • immunotherapy combinations
  • predictive markers
  • immunotherapy targets
  • new immunotherapy combinations

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Published Papers (4 papers)

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Research

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14 pages, 2931 KiB  
Article
HOXA1 3′UTR Methylation Is a Potential Prognostic Biomarker in Oral Squamous cell Carcinoma
by Bruna Pereira Sorroche, Keila Cristina Miranda, Caroline Moraes Beltrami, Lidia Maria Rebolho Batista Arantes, Luiz Paulo Kowalski, Fabio Albuquerque Marchi, Silvia Regina Rogatto and Janete Dias Almeida
Cancers 2024, 16(5), 874; https://doi.org/10.3390/cancers16050874 - 22 Feb 2024
Cited by 1 | Viewed by 1655
Abstract
Background: HOXA1 is a prognostic marker and a potential predictive biomarker for radioresistance in head and neck tumors. Its overexpression has been associated with promoter methylation and a worse prognosis in oral squamous cell carcinoma (OSCC) patients. However, opposite outcomes are also described. [...] Read more.
Background: HOXA1 is a prognostic marker and a potential predictive biomarker for radioresistance in head and neck tumors. Its overexpression has been associated with promoter methylation and a worse prognosis in oral squamous cell carcinoma (OSCC) patients. However, opposite outcomes are also described. The effect of the methylation of this gene on different gene regions, other than the promoter, remains uncertain. We investigated the methylation profile at different genomic regions of HOXA1 in OSCC and correlated differentially methylated CpG sites with clinicopathological data. Methods: The HOXA1 DNA methylation status was evaluated by analyzing data from The Cancer Genome Atlas and three Gene Expression Omnibus datasets. Significant differentially methylated CpG sites were considered with a |∆β| ≥ 0.10 and a Bonferroni-corrected p-value < 0.01. Differentially methylated CpGs were validated by pyrosequencing using two independent cohorts of 15 and 47 OSCC patients, respectively. Results: Compared to normal tissues, we found significantly higher DNA methylation levels in the 3′UTR region of HOXA1 in OSCC. Higher methylation levels in tumor samples were positively correlated with smoking habits and patients’ overall survival. Conclusions: Our findings suggest that HOXA1 gene body methylation is a promising prognostic biomarker for OSCC with potential clinical applications in patient monitoring. Full article
(This article belongs to the Special Issue The Role of Immunotherapy in Squamous Cell Carcinoma)
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14 pages, 2398 KiB  
Article
Response to First-Line Treatment with Immune-Checkpoint Inhibitors in Patients with Advanced Cutaneous Squamous Cell Carcinoma: A Multicenter, Retrospective Analysis from the German ADOReg Registry
by Maximilian Haist, Henner Stege, Berenice Mareen Lang, Aikaterini Tsochataridou, Martin Salzmann, Peter Mohr, Dirk Schadendorf, Selma Ugurel, Jan-Malte Placke, Michael Weichenthal, Ralf Gutzmer, Ulrike Leiter, Martin Kaatz, Sebastian Haferkamp, Carola Berking, Markus Heppt, Barbara Tschechne, Patrick Schummer, Christoffer Gebhardt, Stephan Grabbe and Carmen Loquaiadd Show full author list remove Hide full author list
Cancers 2022, 14(22), 5543; https://doi.org/10.3390/cancers14225543 - 11 Nov 2022
Cited by 5 | Viewed by 2552
Abstract
Cutaneous squamous cell carcinoma (cSCC) is a common malignancy of the skin and has an overall favorable outcome, except for patients with an advanced stage of the disease. The efficacy of checkpoint inhibitors (CPI) for advanced cSCC has been demonstrated in recent clinical [...] Read more.
Cutaneous squamous cell carcinoma (cSCC) is a common malignancy of the skin and has an overall favorable outcome, except for patients with an advanced stage of the disease. The efficacy of checkpoint inhibitors (CPI) for advanced cSCC has been demonstrated in recent clinical studies, but data from real-world cohorts and trial-ineligible cSCC patients are limited. We retrospectively investigated patients with advanced cSCC who have been treated with CPI in a first-line setting at eight German skin cancer centers registered within the multicenter registry ADOReg. Clinical outcome parameters including response, progression-free (PFS) and overall survival (OS), time-to-next-treatment (TTNT), and toxicity were analyzed and have been stratified by the individual immune status. Among 39 evaluable patients, the tumor response rate (rwTRR) was 48.6%, the median PFS was 29.0 months, and the median OS was not reached. In addition, 9 patients showed an impaired immune status due to immunosuppressive medication or hematological diseases. Our data demonstrated that CPI also evoked tumor responses among immunocompromised patients (rwTRR: 48.1 vs. 50.0%), although these responses less often resulted in durable remissions. In line with this, the median PFS (11 vs. 40 months, p = 0.059), TTNT (12 months vs. NR, p = 0.016), and OS (29 months vs. NR, p < 0.001) were significantly shorter for this patient cohort. CPI therapy was well tolerated in both subcohorts with 15% discontinuing therapy due to toxicity. Our real-world data show that first-line CPI therapy produced strong and durable responses among patients with advanced cSCC. Immunocompromised patients were less likely to achieve long-term benefit from anti-PD1 treatment, despite similar tumor response rates. Full article
(This article belongs to the Special Issue The Role of Immunotherapy in Squamous Cell Carcinoma)
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13 pages, 1303 KiB  
Article
Differences and Similarities in the Pattern of Early Metabolic and Morphologic Response after Induction Chemo-Immunotherapy versus Induction Chemotherapy Alone in Locally Advanced Squamous Cell Head and Neck Cancer
by Michael Beck, Sabine Semrau, Marlen Haderlein, Antoniu-Oreste Gostian, Julius Hartwich, Sarina Müller, Annett Kallies, Carol-Immanuel Geppert, Miriam Schonath, Florian Putz, Udo Gaipl, Benjamin Frey, Marc Saake, Heinrich Iro, Michael Uder, Arndt Hartmann, Torsten Kuwert, Rainer Fietkau, Markus Eckstein and Markus Hecht
Cancers 2022, 14(19), 4811; https://doi.org/10.3390/cancers14194811 - 30 Sep 2022
Cited by 2 | Viewed by 2464
Abstract
Background: In head and neck cancer patients, parameters of metabolic and morphologic response of the tumor to single-cycle induction chemotherapy (IC) with docetaxel, cis- or carboplatin are used to decide the further course of treatment. This study investigated the effect of adding a [...] Read more.
Background: In head and neck cancer patients, parameters of metabolic and morphologic response of the tumor to single-cycle induction chemotherapy (IC) with docetaxel, cis- or carboplatin are used to decide the further course of treatment. This study investigated the effect of adding a double immune checkpoint blockade (DICB) of tremelimumab and durvalumab to IC on imaging parameters and their significance with regard to tumor cell remission. Methods: Response variables of 53 patients treated with IC+DICB (ICIT) were compared with those of 104 who received IC alone. Three weeks after one cycle, pathologic and, in some cases, clinical and endoscopic primary tumor responses were evaluated and correlated with a change in 18F-FDG PET and CT/MRI-based maximum-standardized uptake values (SUVmax) before (SUVmaxpre), after treatment (SUVmaxpost) and residually (resSUVmax in % of SUVmaxpre), and in maximum tumor diameter (Dmax) before (Dmaxpre) and after treatment (Dmaxpost) and residually (resD). Results: Reduction of SUVmax and Dmax occurred in both groups; values were SUVmaxpre: 14.4, SUVmaxpost: 6.6, Dmaxpre: 30 mm and Dmaxpost: 23 mm for ICIT versus SUVmaxpre: 16.5, SUVmaxpost: 6.4, Dmaxpre: 21 mm, and Dmaxpost: 16 mm for IC alone (all p < 0.05). ResSUVmax was the best predictor of complete response (IC: AUC: 0.77; ICIT: AUC: 0.76). Metabolic responders with resSUVmax ≤ 40% tended to have a higher rate of CR to ICIT (88%; n = 15/17) than to IC (65%; n = 30/46; p = 0.11). Of the metabolic nonresponders (resSUVmax > 80%), 33% (n = 5/15) achieved a clinical CR to ICIT versus 6% (n = 1/15) to IC (p = 0.01). Conclusions: ICIT and IC quickly induce a response and 18F-FDG PET is the more accurate modality for identifying complete remission. The rate of discrepant response, i.e., pCR with metabolic nonresponse after ICIT was >30%. Full article
(This article belongs to the Special Issue The Role of Immunotherapy in Squamous Cell Carcinoma)
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Review

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16 pages, 727 KiB  
Review
Recent Advances in Immunotherapy for Patients with Head and Neck Cutaneous Squamous Cell Carcinoma
by Adam Khorasanchi, Richard Wu, Kari Kendra and Claire Verschraegen
Cancers 2022, 14(21), 5325; https://doi.org/10.3390/cancers14215325 - 29 Oct 2022
Cited by 4 | Viewed by 2530
Abstract
Cutaneous squamous cell carcinoma (CSCC) is the second most common non-melanoma skin cancer. A majority of patients present with localized disease, but some can present with locally advanced or metastatic disease. Most of these advanced cases occur in the anatomical head and neck [...] Read more.
Cutaneous squamous cell carcinoma (CSCC) is the second most common non-melanoma skin cancer. A majority of patients present with localized disease, but some can present with locally advanced or metastatic disease. Most of these advanced cases occur in the anatomical head and neck region and are associated with more aggressive disease, necessitating prompt and effective treatment. Prior to the emergence of immunotherapy, systemic treatment options were limited to platinum-based chemotherapy and salvaged with targeted epidermal growth factor therapy. These therapies were associated with poor efficacy and increased toxicity in an often frail, older population. Immunotherapy has dramatically improved outcomes in this patient population due to its favorable side effect profile, durable treatment response, and improved overall outcomes. In this review, an overview of the recent advances of immunotherapy in the management of CSCC in the anatomical head and neck region is provided, with a focus on advanced presentations. Full article
(This article belongs to the Special Issue The Role of Immunotherapy in Squamous Cell Carcinoma)
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