Combined Effect of IL-12Rβ2 and IL-23R Expression on Prognosis of Patients with Laryngeal Cancer

Abstract

Background/Aims: This study aimed to pathologically elucidate the roles of interleukin-12 receptor (IL-12R) β2 and interleukin-23 receptor (IL-23R) expression in tumor cells and tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment and to determine their combined effect on prognosis of laryngeal cancer (LC). Methods: The tumor-cell expression scores and TIL positivity ratiosof IL-12Rβ2 and IL-23R in matched LC and normal laryngeal tissue samples from 61 LC patients were measured via immunohistochemistry (IHC). We adopted a linear regression model to analyze the correlation between IL-12Rβ2 and IL-23R expression in tumor cells and TIL ratios. TheKaplan-Meier log-rank test and Cox regression hazard ratios were used to analyze survival. Results: LC tumor cells had a higher IL-12Rβ2 expression and TIL ratio than IL-23R expression and TIL ratio. The significant correlations between IL-12Rβ2 and IL-23R expression and TIL ratios were identified in LC tissues, particularly in well-differentiated LC. Furthermore, either high tumor cell IL-12Rβ2 or low IL-23R expression had better survival than its corresponding low or high expression, respectively. Similar results did for IL-12Rβ2 ratio and IL-23R ratio. Finally, patients with both high IL-12Rβ2 and low IL-23R had the best prognosis among any other combined groups with both gene expression (HR, 0.1; 95% CI, 0.0-0.8). Likewise, patients with positive ratios of high IL-12Rβ2 and low IL-23R TILs had the best survival (HR, 0.1; 95% CI, 0.0-0.4). Conclusion: IL-12Rβ2 and IL-23R create a homeostasis within the tumor cells and TILs, and this homeostasis affects prognosis. While the intrinsic mechanisms of epigenetic immunoediting for IL-12Rβ2 and IL-23R remain unknown, additional larger and functional studies are warranted for validation.

IL-12 Family Cytokines in Cancer and Immunotherapy

“…As one example, IL-23 induced the activation of STAT3 in lung cancer cells expressing IL-23R and stimulated their proliferation [77]. The expression of IL-12Rβ2 and IL-23R on laryngeal tumor cells mediated crosstalk between the cancer cells and tumor-infiltrating lymphocytes and affected the prognosis of laryngeal cancer patients [78]. Furthermore, the expression of IL-23R on B-acute lymphoblastic leukemia (B-ALL) cells in B-ALL patients was increased compared to normal B-lymphocytes and acted to upregulate miR15a and downregulate the pro-survival factor BCL2 [79].…”

Prognostic value of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in laryngeal cancer: What should we expect from a meta-analysis?

“…Tumor-related inflammatory markers have become a focus of many researchers. Previous studies have identified that lymphocyte-to-monocyte ratio, interleukin-12 receptor, immune-inflammatory index and the interleukin-23 receptor can be prognostic indicators for laryngeal cancer ( 12 , 13 ). High neutrophil/lymphocyte level and low lymphocyte level are closely related to tumor invasion and progression ( 14 – 16 ).…”

Antibody-mediated blockade of the IL23 receptor destabilizes intratumoral regulatory T cells and enhances immunotherapy

“…The IL23R, a member of the IL12 cytokine receptor family, is composed of an IL23R alpha chain and a signaling chain (IL12Rβ1) that is shared with the IL12 receptor (IL12R) ( 12 , 13 ). Although the IL23R−STAT3 pathway is the central element in functional T–helper cell 17 (Th17) development ( 14 , 15 ), expression of the IL23R by tumor-infiltrating Treg has been linked to poor prognosis ( 16 – 19 ).…”