The clinical implications of antitumor immunity in head and neck cancer

Abstract

Recent developments have renewed interest in understanding the interaction between transformed cells and the immune system in the tumor microenvironment. Here, we provide a comprehensive review addressing the basics of tumor immunology in relation to head and neck cancer and the cellular components potentially involved in antitumor immune responses. In addition, we describe the mechanisms by which head and neck cancer cells escape immune-mediated killing and progress to form clinically significant disease. Further, we detail what effects standard anticancer therapies may have on antitumor immune responses and how these responses may be altered by current and investigational immunotherapies. Finally, we discuss future directions that need to be considered in the development of new immunotherapeutics designed to durably alter the immune response in favor of the host.

Overcoming barriers to effective immunotherapy: MDSCs, TAMs, and Tregs as mediators of the immunosuppressive microenvironment in head and neck cancer

“…The ability to characterize the overall immune status of large cohorts of tumors has been aided by genomic sequencing and array profiling techniques [1,6], but is still handicapped by tumor sampling and difficulties analyzing representative tissue from a heterogeneous source. In its most basic form, immunosuppression within the TME is mediated directly by HNSCC tumor cells or indirectly by the stroma or through recruitment and polarization of host cells [10,16,18]. All of these factors are important, and ultimately the immunogenicity of an individual HNSCC tumor (and subsequent response to immune-activating therapies) is determined by the balance between recruitment and activation of innate and antigen-specific effector immune cells, and immunosuppressive forces levied by tumor, stromal and other infiltrating immune cells.…”

“…These include cytotoxic immune cells required for an effective immune response, but also include many types of immunosuppressive immune cells. Immature or naïve immune cells that are highly plastic can be polarized into an immunosuppressive phenotype by the cytokine milieu within the TME after their recruitment [10,16]. Well-characterized cell subsets are discussed here.…”

“…Mechanisms of immune escape can be divided into lack of initial activation of an anti-tumor immune response and/or suppression of an activated response. Although both mechanisms are likely crucial to tumor development and progression, the majority of HNSCCs demonstrate measurable infiltration of effector immune cells suggesting the presence of immune suppression within the tumor microenvironment (TME) [6,8,16]. Perhaps even more critically, these same mechanisms of immunosuppression that allow an upper aerodigestive tract malignancy to develop and progress are likely the same that confer resistance to immune activating treatments.…”

Expression of CXCL10 is associated with response to radiotherapy and overall survival in squamous cell carcinoma of the tongue

“…hypoxia and expression of DNA repair genes) [6–9]. The potential of the natural immune response for improving response to conventional treatments has recently been in focus [10–12]. The goal is to enhance the anti-tumoural specific response, which can be achieved either by nonspecific or specific stimulation of the immune system.…”

A phase I dose escalation trial of MAGE-A3- and HPV16-specific peptide immunomodulatory vaccines in patients with recurrent/metastatic (RM) squamous cell carcinoma of the head and neck (SCCHN)

“…For example, SCCHN cells can secrete immunosuppressive cytokines such as TGF-B, IL-10, and prostaglandin E2 (PGE2). [32, 33] Additionally, tumor expression of B7-H1 (PD-L1) which inhibits the activity of PD-1 expressing CD4 and CD8 T cells, has been shown to be expressed in 40-70% of SCCHN patients with higher expression in HPV positive patients. [34-36] Furthermore, in HPV positive SCCHN, early viral oncogenes E5, E6 and E7 can down regulate antigen processing and presentation.…”