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Tumor Microenvironment and Immunotherapy in Head and Neck Cancer

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 5895

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Special Issue Editor

Dr. Marco Carlo Merlano

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Chair, Head and Neck Cancer Multidisciplinary Team, Department of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, 10060 Turin, Italy
Interests: cancer immunology; antibody-dependent cell cytotoxicity; immunotherapy; head and neck cancer; translational research
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Dear Colleagues,

The tumor microenvironment consists of tumor cells, immunological cells, stromal cells and endothelial cells. All of these components interact with each other directly through cell-to-cell contact or through messengers such as interleukins, cytokines, growth factors and chemokines. The tumor microenvironment drives cancer immune phenotype and allows for the identification of inflamed tumors, excluded tumors and deserted tumors.

In head and neck cancer (HNC), the predominant immune phenotype is related to the etiology of the tumor: smoking or virus. However, all the three phenotypes may be represented regardless of etiology. This implies that the first step to approach HNC is to identify which immunophenotype we are facing. Indeed, each phenotype shows distinctive escape mechanisms. Consequently, each immunophenotype requires the reactivation or the inhibition of distinct immune pathways. Therefore, the best immunotherapy approach to head and neck cancer depends on the dominant escape mechanism which, in turn, links to the immune phenotype. For instance, immune check-point inhibitors are more efficient in inflamed tumors, but almost completely inefficient in desert tumors.

In conclusion, the challenge of immunotherapy in HNC is first of all to identify the immunophenotype of the single tumor we are facing; second, to identify potential specific targets of the phenotype; third, to develop drugs directed against the targets; and finally, to test the drug(s) in clinical practice. The goal is to lead to a more informed use of immunotherapy, better selecting the patients to be treated and with which drug. This special issue is focused on the recent scientific progresses achieved in this field.

Dr. Marco Carlo Merlano
Guest Editor

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Keywords

tumor microenvironment
immunotherapy
head and neck cancer
inflamed tumors
excluded tumors
desert tumors

Published Papers (3 papers)

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Research

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13 pages, 2782 KiB

Open AccessArticle

PD1⁺CD8⁺ Cells Are an Independent Prognostic Marker in Patients with Head and Neck Cancer

by Barbora Pokrývková, Marek Grega, Jan Klozar, Ondřej Vencálek, Jaroslav Nunvář and Ruth Tachezy

Biomedicines 2022, 10(11), 2794; https://doi.org/10.3390/biomedicines10112794 - 3 Nov 2022

Cited by 2 | Viewed by 1610

Abstract

Head and neck squamous cell carcinomas (HNSCCs) belong to a group of diverse tumors, which can be induced by infection with human papillomavirus (HPV) or tobacco and alcohol consumption. The viral etiology of HNSCC relates to better clinical outcomes reflecting a different immune system response. Here, we retrospectively analyzed 97 tissue samples from oral and oropharyngeal carcinomas associated and non-associated with HPV infection using multispectral fluorescent immunohistochemistry. To evaluate the immune cell infiltration in tumor and stroma compartments, we designed four panels of four to five antibodies. We detected more T lymphocytes in the stroma, compared to the tumor parenchyma. In HPV positive (HPV⁺) in comparison to HPV negative (HPV⁻) tumors, higher counts of CD3⁺CD4⁺, CD3⁺CD8⁺, PD1⁺CD4⁺, PD1⁺CD8⁺ T cells, and ICOS⁻ Treg cells were detected while more ICOS⁺ Treg cells and CTLA4⁺CD4⁺ T cells were observed in HPV⁻ than in HPV⁺ tumors. The results of the univariate and multivariate analyses confirmed the predominant impact of HPV status on prognosis. More importantly, the number of CD8⁺PD-1⁺ T cells was identified as an independent factor, influencing the overall and/or disease-specific survival of patients with oral cavity or oropharyngeal carcinomas. Full article

(This article belongs to the Special Issue Tumor Microenvironment and Immunotherapy in Head and Neck Cancer)

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25 pages, 3754 KiB

Open AccessArticle

Genomic and Immune Approach in Platinum Refractory HPV-Negative Head and Neck Squamous Cell Carcinoma Patients Treated with Immunotherapy: A Novel Combined Profile

by Silvia Mezi, Giulia Pomati, Ilaria Grazia Zizzari, Alessandra Di Filippo, Bruna Cerbelli, Alessio Cirillo, Giulia Fiscon, Sasan Amirhassankhani, Valentino Valentini, Marco De Vincentiis, Alessandro Corsi, Cira Di Gioia, Vincenzo Tombolini, Carlo Della Rocca, Antonella Polimeni, Marianna Nuti, Paolo Marchetti and Andrea Botticelli

Biomedicines 2022, 10(11), 2732; https://doi.org/10.3390/biomedicines10112732 - 28 Oct 2022

Cited by 3 | Viewed by 1586

Abstract

Introduction: Only a minority of patients with platinum refractory head and neck squamous cell carcinoma (PR/HNSCC) gain some lasting benefit from immunotherapy. Methods: The combined role of the comprehensive genomic (through the FoundationOne Cdx test) and immune profiles of 10 PR/HNSCC patients treated with the anti-PD-1 nivolumab was evaluated. The immune profiles were studied both at baseline and at the second cycle of immunotherapy, weighing 20 circulating cytokines/chemokines, adhesion molecules, and 14 soluble immune checkpoints dosed through a multiplex assay. A connectivity map was obtained by calculating the Spearman correlation between the expression profiles of circulating molecules. Results: Early progression occurred in five patients, each of them showing TP53 alteration and three of them showing a mutation/loss/amplification of genes involved in the cyclin-dependent kinase pathway. In addition, ERB2 amplification (1 patient), BRCA1 mutation (1 patient), and NOTCH1 genes alteration (3 patients) occurred. Five patients achieved either stable disease or partial response. Four of them carried mutations in PI3K/AKT/PTEN pathways. In the only two patients, with a long response to immunotherapy, the tumor mutational burden (TMB) was high. Moreover, a distinct signature, in terms of network connectivity of the circulating soluble molecules, characterizing responder and non-responder patients, was evidenced. Moreover, a strong negative and statistically significant (p-value ≤ 0.05) correlation with alive status was evidenced for sE-selectin at T1. Conclusions: Our results highlighted the complexity and heterogeneity of HNSCCs, even though it was in a small cohort. Molecular and immune approaches, combined in a single profile, could represent a promising strategy, in the context of precision immunotherapy. Full article

(This article belongs to the Special Issue Tumor Microenvironment and Immunotherapy in Head and Neck Cancer)

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Review

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12 pages, 1604 KiB

Open AccessReview

How Chemotherapy Affects the Tumor Immune Microenvironment: A Narrative Review

by Marco Carlo Merlano, Nerina Denaro, Danilo Galizia, Fiorella Ruatta, Marcella Occelli, Silvia Minei, Andrea Abbona, Matteo Paccagnella, Michele Ghidini and Ornella Garrone

Biomedicines 2022, 10(8), 1822; https://doi.org/10.3390/biomedicines10081822 - 28 Jul 2022

Cited by 12 | Viewed by 2364

Abstract

Chemotherapy is much more effective in immunocompetent mice than in immunodeficient ones, and it is now acknowledged that an efficient immune system is necessary to optimize chemotherapy activity and efficacy. Furthermore, chemotherapy itself may reinvigorate immune response in different ways: by targeting cancer cells through the induction of cell stress, the release of damage signals and the induction of immunogenic cell death, by targeting immune cells, inhibiting immune suppressive cells and/or activating immune effector cells; and by targeting the host physiology through changes in the balance of gut microbiome. All these effects acting on immune and non-immune components interfere with the tumor microenvironment, leading to the different activity and efficacy of treatments. This article describes the correlation between chemotherapy and the immune changes induced in the tumor microenvironment. Our ultimate aim is to pave the way for the identification of the best drugs or combinations, the doses, the schedules and the right sequences to use when chemotherapy is combined with immunotherapy. Full article

(This article belongs to the Special Issue Tumor Microenvironment and Immunotherapy in Head and Neck Cancer)

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