br There is increasing evidence that TAM accumulation is ass
There is increasing evidence that TAM accumulation is associated with poor clinical prognosis and resistance to cancer therapy, which is in part due to the immunosuppressive and tumor-promoting activities of TAMs (Cassetta and Pollard, 2018). Recently, several studies on TAM-targeting cancer therapy have concentrated on the following strategies: the inhibition of macrophage recruitment, conversion of pro-tumorigenic M2 to the antitumor M1 phenotype, and suppression of TAM survival (Cassetta and Pollard, 2018). Because the classical M1 macrophage possesses antitumor activity, the polarization from tumor-promoting M2 to tumoricidal M1 macrophages appears to be a better potential target for cancer therapy. Thus, the re-education of TAMs plasticity via adrenergic signaling could block the pro-tumorigenic ef-fects of TAMs. Recent clinical research has supported the hypothesis of using β-blockers to reduce the rates of disease progression and improve overall survival in locally advanced NSCLC (Wang et al., 2013). More recently, a targetable mechanism of EGFR inhibitor resistance eluci-dated that chronic stress hormones promote EGFR TKI resistance via β-AR signaling by an LKB1/CREB/IL-6-dependent mechanism and sug-gested that the combination of β-blockers with EGFR TKIs merit further investigation as a strategy to abrogate resistance (Nilsson et al., 2017). In rodent animal models, reducing β-adrenergic signaling facilitates the conversion of tumors to an immunologically active tumor micro-environment with an increased intratumoral frequency of CD8+ T KPT330 and a decreased expression of programmed death receptor-1 (PD-1), inducing a shift in antitumor immunity (Bucsek et al., 2017).
Accumulating evidence supports the assertion that catecholamine-mediated adrenergic pathways potentiate the neuro-immune-tumor interactions. Our results show that macrophages play a crucial role in connecting neural signals and immune response, wherein the inhibition of adrenergic nerves shifts the active state of macrophages to block angiogenesis and reshapes the immunosuppressive microenvironment that supports aggressive lung cancer. Identifying and targeting the neuro-immune axis that improve therapeutic eﬃcacy by bolstering anti-tumor responses lays the groundwork for the translation of adre-nergic blockade as a promising adjuvant to existing therapeutic stra-tegies in clinical oncology.
5. Financial support
Declaration of Competing Interest
All authors in this manuscript declare no conflict of interest.
Appendix A. Supplementary data
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11 Original Article
Cathelicidin Suppresses Colon Cancer Metastasis via a P2RX7-Dependent Mechanism
Jiani Wang,1,2 Michelle Cheng,2 Ivy K.M. Law,2 Christina Ortiz,2 Mingjun Sun,1 and Hon Wai Koon2
1Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, China; 2Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA