Transcriptional and non-transcriptional roles of LXRs in cancer cells

Liver X Receptors (LXRs) have been proposed to have some anticancer properties. LXRs affect cancer cell proliferation and cell death through mechanisms that seems mostly to rely on its transcriptional activities. We recently identified a new non-genomic role of LXR? in colon cancer cells. Under LXR agonist treatment, LXR? induces an atypical cell death called pyroptosis in vitro and in vivo. Together with other reports, we raise the importance of targeting LXRs in cancer treatment

Production of Adenosine by Ectonucleotidases: A Key Factor in Tumor Immunoescape

It is now well known that tumor immunosurveillance contributes to the control of cancer growth. Many mechanisms can be used by cancer cells to avoid the antitumor immune response. One such mechanism relies on the capacity of cancer cells or more generally of the tumor microenvironment to generate adenosine, a major molecule involved in antitumor T cell response suppression. Adenosine is generated by the dephosphorylation of extracellular ATP released by dying tumor cells. The conversion of ATP into adenosine is mediated by ectonucleotidase molecules, namely, CD73 and CD39. These molecules are frequently expressed in the tumor bed by a wide range of cells including tumor cells, regulatory T cells, Th17 cells, myeloid cells, and stromal cells. Recent evidence suggests that targeting adenosine by inhibiting ectonucleotidases may restore the resident antitumor immune response or enhance the efficacy of antitumor therapies. This paper will underline the impact of adenosine and ectonucleotidases on the antitumor response

Transcriptional and non-transcriptional roles of LXRs in cancer cells

Liver X Receptors (LXRs) have been proposed to have some anticancer properties. LXRs affect cancer cell proliferation and cell death through mechanisms that seems mostly to rely on its transcriptional activities. We recently identified a new non-genomic role of LXRβ in colon cancer cells. Under LXR agonist treatment, LXRβ induces an atypical cell death called pyroptosis in vitro and in vivo. Together with other reports, we raise the importance of targeting LXRs in cancer treatment

Interleukin-1β and Cancer

Within a tumor, IL-1β is produced and secreted by various cell types, such as immune cells, fibroblasts, or cancer cells. The IL1B gene is induced after “priming” of the cells and a second signal is required to allow IL-1β maturation by inflammasome-activated caspase-1. IL-1β is then released and leads to transcription of target genes through its ligation with IL-1R1 on target cells. IL-1β expression and maturation are guided by gene polymorphisms and by the cellular context. In cancer, IL-1β has pleiotropic effects on immune cells, angiogenesis, cancer cell proliferation, migration, and metastasis. Moreover, anti-cancer treatments are able to promote IL-1β production by cancer or immune cells, with opposite effects on cancer progression. This raises the question of whether or not to use IL-1β inhibitors in cancer treatment

STAT3, a Master Regulator of Anti-Tumor Immune Response

Immune cells in the tumor microenvironment regulate cancer growth. Thus cancer progression is dependent on the activation or repression of transcription programs involved in the proliferation/activation of lymphoid and myeloid cells. One of the main transcription factors involved in many of these pathways is the signal transducer and activator of transcription 3 (STAT3). In this review we will focus on the role of STAT3 and its regulation, e.g., by phosphorylation or acetylation in immune cells and how it might impact immune cell function and tumor progression. Moreover, we will review the ability of STAT3 to regulate checkpoint inhibitors

Tumor Immunogenic Cell Death as a Mediator of Intratumor CD8 T-Cell Recruitment

The success of anticancer treatments relies on a long-term response which can be mediated by the immune system. Thus, the concept of immunogenic cell death (ICD) describes the capacity of dying cancer cells, under chemotherapy or physical stress, to express or release danger-associated molecular patterns (DAMPs). These DAMPs are essential to activate dendritic cells (DCs) and to stimulate an antigen presentation to CD8 cytotoxic cells. Then, activated CD8 T cells exert their antitumor effects through cytotoxic molecules, an effect which is transitory due to the establishment of a feedback loop leading to T-cell exhaustion. This phenomenon can be reversed using immune checkpoint blockers (ICBs), such as anti-PD-1, PD-L1 or CTLA-4 Abs. However, the blockade of these checkpoints is efficient only if the CD8 T cells are recruited within the tumor. The CD8 T-cell chemoattraction is mediated by chemokines. Hence, an important question is whether the ICD can not only influence the DC activation and resulting CD8 T-cell activation but can also favor the chemokine production at the tumor site, thus triggering their recruitment. This is the aim of this review, in which we will decipher the role of some chemokines (and their specific receptors), shown to be released during ICD, on the CD8 T-cell recruitment and antitumor response. We will also analyze the clinical applications of these chemokines as predictive or prognostic markers or as new targets which should be used to improve patients’ response