Impact of Age on Disease Progression and Microenvironment in Oral Cancer

Abstract

Despite the recognized link between aging and cancer, most preclinical studies in experimental tumor models are conducted with 6- to 8-wk-old rodents. The goal of the present study was to examine the impact of age on tumor incidence, growth, and microenvironmental characteristics in mouse models of head and neck squamous cell carcinoma (HNSCC). Experimental studies were conducted with the 4-nitroquinoline-oxide (4NQO) oral carcinogenesis model and orthotopic FaDu HNSCC xenografts, established in young (7 to 12 wk of age) and old (65 to 70 wk of age) female C57BL/6 mice ( n = 44; 4NQO model) and severe combined immunodeficient mice ( n = 13; HNSCC xenografts). Noninvasive whole body magnetic resonance imaging revealed increased subcutaneous and visceral fat in aging animals of both strains. On histologic examination, a higher incidence ( P < 0.001) of severe dysplasia/invasive squamous cell carcinoma was observed in old mice (92%) as compared with young mice (69%). Old C57BL/6 mice exposed to 4NQO exhibited increased incidence of oral and extraoral (peritoneal masses) neoplasms (42%) versus their young counterparts ( P < 0.05). The incidence of extraoral neoplasms was significantly lower (16%) in the younger cohort. Interestingly, no difference in growth rate and oxygen saturation was observed between orthotopic FaDu xenografts established in old and young severe combined immunodeficient mice. Our observations suggest that host age may have an impact on the growth kinetics and progression of HNSCC in the immunocompetent 4NQO model. Further investigation into the impact of aging on tumor response to preventive and therapeutic intervention is warranted.

The role of dectin-1 signaling in altering tumor immune microenvironment in the context of aging

“…S1). These data are consistent with a previous study that elegantly showed similar results in aged mice [27]. Since aging-related differences in OSCC were not significant after 23-24 weeks, we focused on early events of carcinogenesis in defining altered and accelerated dysplasia in aging mice.…”

The Role of Dectin-1 Signaling in Altering Tumor Immune Microenvironment in the Context of Aging

“…Also, more mice in the aged group showed these changes at early time-points (Figure S1). These data are consistent with a previous study that elegantly showed similar results in aged mice (34). Since agingrelated differences in OSCC were not significant after 23-24 weeks, we focused on early events of carcinogenesis in defining altered and accelerated dysplasia in aging mice.…”

Histological features and survival in young patients with HPV‐negative oral squamous cell carcinoma

“…Another hypothesis is related to the ability of cancer cells to avoid destruction from the host immune system (Chen & Mellman, 2017). Indeed, recent studies have increasingly shown that tumour immune microenvironment plays a critical role in cancer progression, although significant results in young OSCC patients has not yet emerged (Huang et al., 2019; Ryu et al., 2019; Teixeira et al., 2019; Vincent‐Chong et al., 2018).…”