Abstract
Oral premalignant lesions (OPLs) are the precursors to oral cavity cancers, and have variable rates of progression to invasive disease. As an intermediate state, OPLs have acquired a subset of the genomic alterations while arising in an oral inflammatory environment. These specific genomic changes may facilitate the transition to an immune microenvironment that permits malignant transformation. Here, we will discuss mechanisms by which OPLs develop an immunosuppressive microenvironment that facilitates progression to invasive cancer. We will describe how genomic alterations and immune microenvironmental changes co-evolve and cooperate to promote OSCC progression. Finally, we will describe how these immune microenvironmental changes provide specific and unique evolutionary vulnerabilities for targeted therapies. Therefore, understanding the genomic changes that drive immunosuppressive microenvironments may eventually translate into novel biomarker and/or therapeutic approaches to limit the progression of OPLs to potential lethal oral cancers.
Highlights
Oral squamous cell carcinomas (OSCCs) involving the tongue, cheek, gums, and other sites of the mouth are the most common form of head and neck cancer (HNSCC), responsible for over 377,000 new cases and 177,000 deaths per year worldwide [1]
As mutations and other genetic alterations accumulate, oral premalignant lesions (OPLs) become progressively infiltrated with immune suppressive myeloid cells including myeloid-derived suppressor cells (MDSC), M2 tumor-associated macrophages (TAM) and regulatory T cells (Treg; Figure 1)
We have shown an important role for tumorexpressed inducible nitric oxide synthase (iNOS) in orchestrating the induction of tumorinfiltrating myeloid cells and acquisition of MDSC suppressive function in established cancer [39, 44]
Summary
Oral squamous cell carcinomas (OSCCs) involving the tongue, cheek, gums, and other sites of the mouth are the most common form of head and neck cancer (HNSCC), responsible for over 377,000 new cases and 177,000 deaths per year worldwide [1]. The precursors to OSCC are oral premalignant lesions (OPLs) that affect approximately 4.5% of the world’s population [2]. It is likely that the genomic alterations cooperate and co-regulate the immune microenvironment in OPLs to facilitate the progression of OPLs to invasive cancer [1, 5]. Inflammatory changes in the immune microenvironment may promote genomic instability within OPLs. Here, we will discuss the how OPLs develop an immunosuppressive microenvironment that facilitates progression to invasive cancer. We will describe how the genomic context of premalignant lesions may provide specific and unique evolutionary vulnerabilities for targeted therapies. Pursuit of such paradigms may eventually translate into novel biomarker and/or therapeutic use
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