A new role for NFκB in immunosurveillance and its implications for cancer immunotherapy

Abstract

The activation of NFκB in the tumor microenvironment is associated with inflammatory responses that promote disease progression. We have recently found that the activation of NFκB in the tumor also regulates T cell-mediated immune responses, hence actively participating in cancer immunosurveillance. These findings call for reassessment of the function of NFκB within neoplastic lesions and open novel perspectives for anticancer immunotherapy.

Keywords: Immunotherapy; NFκB; chemokines; immunosurveillance; inflammation; lung cancer.

Figure 1. Potential mechanisms involved in the pro- and anti-tumor functions of NFκB. The activation of NFκB by oncogenes or pro-inflammatory cytokines drives the expression of pro-inflammatory mediators including factors that recruit myeloid cells such as chemokine (C-X-C motif) ligand (CXCL)1/3 and interleukin-8 (IL-8). Upon recruitment, myeloid-derived suppressor cells (MDSC) may dampen antitumor immune responses. In addition, multiple chemokines may directly stimulate angiogenesis and metastatic dissemination. Conversely, in the presence of cytokines such as interferon (IFN)γ, which may be produced by natural killer (NK) or T cells, NF-κB may cooperate with IFNγ-induced transcription factors to stimulate the secretion of high levels of T cell-recruiting chemokines, such as CXCL9–11. Besides promoting tumor infiltration by antitumor cytotoxic T cells, these factors may also exert direct anti-angiogenic effects.