Cetuximab immunotherapy targeting the epidermal growth factor receptor (EGFR) has been used to treat nasopharyngeal cancer (NPC) with some success. Therefore, combining an immune adjuvant to boost the immune microenvironment may improve its clinical efficacy. Herein, we investigate the immune-stimulatory effects of Poly-ICLC (a TLR3 agonist) in enhancing cetuximab-based immunotherapy and correlate these responses with FcɣRIIIa (V158F) or TLR3 single nucleotide polymorphisms (SNPs-L412F and C829T) expressed on immune effector cells. We observed high levels of TLR3 mRNA in NPC cells; and both TLR3 and EGFR expression were unaffected by Poly-ICLC treatment. Cetuximab plus Poly-ICLC significantly enhanced NK-mediated ADCC through up-regulation of CD107a and Granzyme B expression. This effect was independent of FcɣRIIIa-V158F and TLR3-L412F or TLR3-C829T polymorphisms expressed on NK cells. Additionally, IFN-ɣ expression and secretion were doubled following cetuximab plus poly-ICLC treatment; compared to either treatment alone. This effect was independent of TLR3 polymorphisms. Consequentially, adaptive immune responses were also seen with increased DC maturation (CD83), costimulatory molecules expression (CD80 and CD86) and increased frequency of EGFR-specific CD8 + T cells following Poly-ICLC treatment. The percentage of CD80+ CD83+ and CD83+ CD86+ DC was highest in the Poly-ICLC plus cetuximab group, compared to either treatment alone. These results demonstrate the effectiveness of Poly-ICLC in enhancing both cetuximab-mediated innate and adaptive anti-tumor immunity against NPC, which is independent of FcɣRIIIa-158, TLR3-L412F or TLR3-C829T polymorphisms. Additionally, Poly-ICLC does not downregulate EGFR expression on NPC cells and hence, will not dampen cetuximab anti-tumor activity.
Near-infrared (NIR) Raman spectroscopy has been investigated as a tool to differentiate nasopharyngeal cancer (NPC) from normal nasopharyngeal tissue in an ex-vivo setting. Recently, we have miniaturized the fiber-optic Raman probe to investigate its utility in real time in-vivo surveillance of NPC patients. A posterior probability model using partial linear square (PLS) mathematical technique was constructed to verify the sensitivity and specificity of Raman spectroscopy in diagnosing NPC from post-irradiated and normal tissue using a diagnostic algorithm from three significant latent variables. NIR-Raman signals of 135 sites were measured from 79 patients with either newly diagnosed NPC (N = 12), post irradiated nasopharynx (N = 37) and normal nasopharynx (N = 30). The mean Raman spectra peaks identified differences at several Raman peaks at 853 cm−1, 940 cm−1, 1078 cm−1, 1335 cm−1, 1554 cm−1, 2885 cm−1 and 2940 cm−1 in the three different nasopharyngeal conditions. The sensitivity and specificity of distinguishing Raman signatures among normal nasopharynx versus NPC and post-irradiated nasopharynx versus NPC were 91% and 95%; and 77% and 96% respectively. Real time near-infrared Raman spectroscopy has a high specificity in distinguishing malignant from normal nasopharyngeal tissue in vivo, and may be investigated as a novel non-invasive surveillance tool in patients with nasopharyngeal cancer.
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