Editorial; Immuno-Oncologic Biomarker Signatures for Personalized Immunotherapy and Immunoprevention in Oral Squamous Cell Carcinoma

Rania Hassan Younis^1,2*Ranee Mehra³Nikolaos Nikitakis⁴

• ¹OralPath_DentCare, LLC, Ellicott City, United States
• ²Alexandria University, Alexandria, Egypt
• ³University of Maryland Medical Center, Baltimore, United States
• ⁴Ethniko kai Kapodistriako Panepistemio Athenon, Athens, Greece

The development of oral cancer is a multifactorial and complex process (1). The interaction between the mutated oral epithelial cells and the underlying stromal and immune system plays a major role in the process of tumor development and progression. Immunotherapy represents the most recent therapeutic advent in the field with significant improvement in overall survival. Yet, differential patients' responses warrants more understanding of the immuno-oncologic profile of oral cancer.The current research topic in Frontiers oral health-oral cancer aimed to shed light on recent evidence-based immuno-oncologic biomarkers associated with the clinico-pathological features of oral squamous cell carcinoma (OSCC) and potentially cancerous oral lesions. The ultimate goal is for better patients' stratification, and hence more guidance for personalized therapeutic regimens (2).The topic starts with a research manuscript by Sahu et al, titled: 4-Nitroquinoline 1-oxide induces immune cells death to onset early immunosuppression during Oral Squamous Cell Carcinoma Development. In this manuscript the authors present an in vivo model of how the chemical carcinogen modulates an immunosuppressive profile that starts in the oral precancerous stages. Significant decrease in B and T cell populations, specifically CD5+B cell, and gamma/delta-T cell population (γδ-TCR + ) was observed in the spleen in the early stages of development of the precancerous lesions and persisted after OSCC development. Despite the increase in NK, NKT, and lymphoid DC, in peripheral blood there was a decrease in most of the lymphocyte population (T, B, CD5+B cells) during early development, but not later. Concluding that immune cell derangement is not a post-cancerous event, rather, an early event that may persist until tumor development and beyond. In vitro analysis demonstrated B cells to be more susceptible to reduced viability and DNA damage when expos ed to the chemical carcinogen compared to T cells. These findings provide supportive pre-clinical evidence for introducing immunotherapy in initial stages of precancerous lesions, as a preventive strategy for OSCC.To further highlight the onset of immune derangement early in OSCC precursor lesions, the second research manuscript by Hanroongsri, et al, titled: Expression of PD-L1 and p-RPS6 in epithelial dysplasia and squamous cell carcinoma of the oral cavity, aimed to describe a significant correlation between the expression of the well-established immunologic and oncologic biomarkers, programmed death ligand -1 (PD-L1) and phosphorylated ribosomal protein S6 (RPS6), respectively, in oral epithelial dysplasia (OED). In 52 OSCC and 48 OED cases, p-RPS6 expression was detected in all cases of OSCC and OED, whereas PD-L1 was expressed in 42/48 (87%) OED and in 28/52 (53%) OSCC. The patients with mild OED presented a significantly higher expression of PD-L1 and p-RPS6, when compared to moderately differentiated OSCC patients (P<0.05). They described a significant positive correlation between PD-L1 and p-RPS6 expression in OED and OSCC patients. Their findings suggest that up-regulation of PD-L1 can be related to activation of the mitogenic pathway mTOR in the early events of precancerous lesions as well as in the pathogenesis of OSCC. Their work provides additional supportive evidence that the process of immune modulation can be concurrent with the mitogenic progression of precancerous and tumor cells. Review, the authors included six retrospective cohort studies involving 1,203 patients that met the inclusion criteria. They aimed to explore the tertiary lymphoid structures (TLS) in the tumor microenvironment (TME). TLS were located in the peri-tumoral area (75.4%-84.8%) compared to the intra-tumoral area (33.8%-33.9%). The review showed that the presence of TLS is associated with improved survival in OSCC. They concluded that standardization of methodologies of detecting TLS is imperative to ensure consistency in criteria utilization, thereby facilitating meaningful data comparison. Their work adds to the significance of characterizing tumor inflammation and confirms a long-standing notion among pathologists, that TLS are usually associated with low grade tumors, responsive immune system, or tumors with better prognosis. axis that triggers NF-kB, as a significant driver of tumor growth. They conclude that IL33 may be a prognostic biomarker and therapeutic target in HNSCC, that significantly configures the tumor microenvironment and tumor aggressiveness. They also bring up the role of serum IL33 and ST2, that remains to be further studied in HNSCC, as the soluble form of ST2 may function as a decoy receptor reducing IL-33 biologic activity. This highlights the implications of soluble versus cell bound inflammatory cytokines that may have different biological and translational significance.The five studies presented in the current research topic emphasized traditional, emerging and novel complex biomarker signatures of the immuno-oncologic platform. This area of research focus will help stratify OSCC patients and accordingly open new avenues for better personalized lines of treatment, early detection, and prevention of OSCC.