Recurrent HNSCC Harbor an Immunosuppressive Tumor Immune Microenvironment Suggesting Successful Tumor Immune Evasion

Watermann, Christian; Pasternack, Helen; Idel, Christian; Brägelmann, Johannes; Kuppler, Patrick; Offermann, Anne; Jonigk, Danny; Kühnel, Mark Philipp; Schröck, Andreas; Dreyer, Eva; Rosero, Christian; Nathansen, Jacqueline; Dubrovska, Anna; Tharun, Lars; Kirfel, Jutta; Wollenberg, Barbara; Krupar, Rosemarie

doi:10.1158/1078-0432.ccr-20-0197

Cited by 59 publications

(43 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, in HNSC a negative correlation between CD73 and CD8+ T cell infiltration, including HPV-positive patients was observed ( Figure 4 B). This observation supports a recent study from Watermann et al [ 99 ] demonstrating that recurrent HNSC has an immunosuppressive tumor microenvironment with significant depletion of CD8 tumor-infiltrating lymphocytes (TILs), which was more pronounced following adjuvant chemo-radiotherapy. Therefore, these tumors might be less susceptible to respond to ICIs due to the lack of infiltrating CD8+ CTLs.…”

Section: Cd73 and Tumor Immune Microenvironmentsupporting

confidence: 91%

CD73, Tumor Plasticity and Immune Evasion in Solid Cancers

Yang

Yao

Davis

et al. 2021

Cancers

View full text Add to dashboard Cite

Regulatory networks controlling cellular plasticity, important during early development, can re-emerge after tissue injury and premalignant transformation. One such regulatory molecule is the cell surface ectoenzyme ecto-5′-nucleotidase that hydrolyzes the conversion of extracellular adenosine monophosphate to adenosine (eADO). Ecto-5′-nucleotidase (NT5E) or cluster of differentiation 73 (CD73), is an enzyme that is encoded by NT5E in humans. In normal tissue, CD73-mediated generation of eADO has important pleiotropic functions ranging from the promotion of cell growth and survival, to potent immunosuppression mediated through purinergic G protein-coupled adenosine receptors. Importantly, tumors also utilize several mechanisms mediated by CD73 to resist therapeutics and in particular, evade the host immune system, leading to undesired resistance to targeted therapy and immunotherapy. Tumor cell CD73 upregulation is associated with worse clinical outcomes in a variety of cancers. Emerging evidence indicates a link between tumor cell stemness with a limited host anti-tumor immune response. In this review, we provide an overview of a growing body of evidence supporting the pro-tumorigenic role of CD73 and adenosine signaling. We also discuss data that support a link between CD73 expression and tumor plasticity, contributing to dissemination as well as treatment resistance. Collectively, targeting CD73 may represent a novel treatment approach for solid cancers.

show abstract

Section: Cd73 and Tumor Immune Microenvironmentsupporting

confidence: 91%

CD73, Tumor Plasticity and Immune Evasion in Solid Cancers

Yang

Yao

Davis

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…The tumor immune microenvironment is dynamic and has been shown to be depleted of CD8+ T cells and B lymphocytes in recurrent versus primary tumors, with immune suppressive features apparent after receipt of chemoradiation therapy ( 142 ). Clonal expansion of tumor-infiltrating T cells has been identified in patients with untreated, locoregionally advanced SCCHN ( 93 ).…”

Section: Discussion and Future Directionsmentioning

confidence: 99%

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

2021

View full text Add to dashboard Cite

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.

show abstract

“…In addition to well-established features, including PD-L1 expression, TMB, immune-related gene signatures, MHC and T cell receptor repertoire, clonality of neoantigens and tumor heterogeneity, the balance between immune surveillance and tolerance appears highly context dependent and critically depends on an increasing list of potential variables. These variables include etiological risk factors [157,158], sex differences [159], the microbiome [160], other immune subsets beyond the T cell compartment [161], ternary lymphoid structures [133], the peripheral nervous system [162] and conventional therapeutics [163,164]. These variables should be considered in future explorative and clinical trials addressing the TIME and its alterations during immunotherapy to establish new strategies of combinatorial treatments for HNSCC patients with the final aim to overcome ICI resistance.…”

Section: Discussionmentioning

confidence: 99%

Immune-Related Mutational Landscape and Gene Signatures: Prognostic Value and Therapeutic Impact for Head and Neck Cancer

Feng

Heß

2021

Cancers

View full text Add to dashboard Cite

Immunotherapy by immune checkpoint inhibition has become a main pillar in the armamentarium to treat head and neck cancer and is based on the premise that the host immune system can be reactivated to successfully eliminate cancer cells. However, the response rate remains low and only a small subset of head and neck cancer patients achieves a durable clinical benefit. The availability of multi-omics data and emerging computational technologies facilitate not only a deeper understanding of the cellular composition in the tumor immune microenvironment but also enables the study of molecular principles in the complex regulation of immune surveillance versus tolerance. These knowledges will pave the way to apply immunotherapy more precisely and effectively. This review aims to provide a holistic view on how the immune landscape dictates the tumor fate and vice versa, and how integrative analysis of multi-omics data contribute to our current knowledge on the accuracy of predictive biomarkers and on a broad range of factors influencing the response to immunotherapy in head and neck cancer.

show abstract

Recurrent HNSCC Harbor an Immunosuppressive Tumor Immune Microenvironment Suggesting Successful Tumor Immune Evasion

Cited by 59 publications

References 57 publications

CD73, Tumor Plasticity and Immune Evasion in Solid Cancers

CD73, Tumor Plasticity and Immune Evasion in Solid Cancers

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

Immune-Related Mutational Landscape and Gene Signatures: Prognostic Value and Therapeutic Impact for Head and Neck Cancer

Contact Info

Product

Resources

About