Interleukin-15 expression in lung cancer.

Abstract

e21064 Background: Interleukin-15 (IL-15) is a pro-inflammatory cytokine that stimulates the differentiation and proliferation of T, B, and NK cells. IL-15 is normally tightly bound by its receptor, IL-15Rα. Dendritic cells and monocytes/macrophages primarily express both IL-15 and IL-15-Rα; however, expression has been detected on epithelial cells including those of the lung. In the lung, IL-15 is thought to play a role in the induction of immune responses to infection. Over expression of IL-15 has been shown to induce NK cell activation and cytotoxic T-lymphocyte (CTL) responses leading to tumor regression. Little is known about IL-15 or IL-15Rα expression in lung cancer. Methods: mRNA from 146 primary lung cancers were analyzed by multiplex qPCR for expression of IL-15, IL-15Rα and b-actin (internal control) and compared to expression in normal lung tissue from 45 patients. Of the 146 patients, 50 were stage I (IA=20, IB=30), 49 stage II (IIA=9, IIB=40), 36 stage III (IIIA=18, IIIB=18), and 11 stage IV. Results: Comparing the expression of IL-15 between normal lung and tumor, we found tumors expressed significantly less IL-15 than normal lung (P<0.001). Lung cancers at any given stage, expressed significantly less IL-15 than that seen in normal lung. When comparing stages, stage IV tumors expressed significantly less IL-15 than tumors of stages I (P=0.021), II (P=0.020), or III (P=0.024). There was no difference in expression between stages I, II or III (P>0.05). When examining the expression of IL-15Rα we found no differences between normal lung and tumor. No differences were seen between normal lung and stages I-IIIA; however, significantly less IL-15Rα expression was noted in stages IIIB and IV compared to normal lung. Between stages, stages I and II had significantly more IL-15Rα expression than stage IV tumors. There were no differences between stages I, II and III. Conclusions: Pro-inflammatory cytokines such as IL-15 may be important for the induction of lung immunity. IL-15 expression is down regulated in lung cancers and this down regulation increases with stage. We posit that the down regulation of IL-15 by lung cancers may aid in their evasion of immune responses allowing progression and dissemination of tumor.

CD8+CD57+ T cells exhibit distinct features in human non-small cell lung cancer

“…29 30 We analyzed the link between IL-15 and effector function-associated molecules using RNA-seq data from The Cancer Genome Atlas (TCGA) database, which includes 571 cases adenocarcinoma, 444 cases squamous carcinoma and 109 cases normal lung tissues. We found that the expression level of IL-15 in tumors was significantly lower than that of normal lung tissues (p<0.0001; online supplementary figure S7A), which was consistent with a previous report by Adhami et al 31 Moreover, the expression levels of IL-15 in tumor specimens were strongly correlated with T-cell effector functionassociated molecules such as IFNG, GZMB and PRF1 (online supplementary figure S7B-D). The representative of Ki-67 expression in CD8 + CD57and CD8 + CD57 + T cells from lymph nodes ex vivo (A) (n=5) and after in vitro stimulation with aCD3 and aCD28 mAbs (B) (n=3).…”

A multiobjective Bayesian networks approach for joint prediction of tumor local control and radiation pneumonitis in nonsmall‐cell lung cancer (NSCLC) for response‐adapted radiotherapy

“…For example, IL-10 is able to favor tumor growth both directly by affecting the tumor cells and indirectly by inhibiting immune cells 41 . Interleukin-15 (IL-15), a key pro-inflammatory cytokine 42 , can induce NK cell activation and cytotoxic T-lymphocyte responses leading to tumor regression 43 .…”

“…41 Interleukin-15 (IL-15), a key proinflammatory cytokine, 42 can induce NK cell activation and cytotoxic T-lymphocyte responses leading to tumor regression. 43 PET tumor radiomics can help predict response in NSCLC. 44 Yang et al found that GLSZM-LZLGE exhibited significant temporal changes in partial metabolic responders.…”