Tumor associated macrophages (TAMs) are present in high density in solid tumors. TAMs share many characteristics with alternatively activated macrophages, also called M2. They have been shown to favor tumor development and a role in chemoresistance has also been suggested. Here, we investigated the effects of M2 in comparison to M1 macrophages on cancer cell sensitivity to etoposide. We set up a model of macrophage polarization, starting from THP-1 monocytes differentiated into macrophages using PMA (Phorbol 12-myristate 13-acetate). Once differentiated (M0 macrophages), they were incubated with IL-4 and IL-13 in order to obtain M2 polarized macrophages or with IFN-gamma and LPS for classical macrophage activation (M1). To mimic the communication between cancer cells and TAMs, M0, M1 or M2 macrophages and HepG2 or A549 cancer cells were co-cultured during respectively 16 (HepG2) or 24 (A549) hours, before etoposide exposure for 24 (HepG2) or 16 (A549) hours. After the incubation, the impact of etoposide on macrophage polarization was studied and cancer cell apoptosis was assessed by western-blot for cleaved caspase-3 and cleaved PARP-1 protein, caspase activity assay and FACS analysis of Annexin V and PI staining. mRNA and protein expression of M1 and M2 markers confirmed the polarization of THP-1-derived macrophages, which provide a new, easy and well-characterized model of polarized human macrophages. Etoposide-induced cancer cell apoptosis was markedly reduced in the presence of THP-1 M2 macrophages, while apoptosis was increased in cells co-cultured with M1 macrophages. On the other hand, etoposide did not influence M1 or M2 polarization. These results evidence for the first time a clear protective effect of M2 on the contrary to M1 macrophages on etoposide-induced cancer cell apoptosis.

Tumor-associated macrophages (TAMs) play a central role in tumor progression, metastasis and recurrence after treatment. Macrophage plasticity and diversity allow their classification along a M1 – M2 polarization axis. Tumor–associated macrophages usually display a M2-like phenotype, associated with pro-tumoral features whereas M1 macrophages exert anti-tumor functions. Targeting the reprogramming of TAMs towards M1-like macrophages would thus be an efficient way to promote tumor regression. This can be achieved through therapies including chemotherapy, immunotherapy and radiotherapy. In this review, we first describe how chemo- and immuno-therapies can target TAMs and secondly we detail how radiotherapy modifies macrophage phenotype and present the molecular pathways that may be involved. The identification of irradiation dose inducing macrophage reprogramming and of the underlying mechanisms could lead to the design of novel therapeutic strategies and improve synergy in combined treatments.

A transmembrane protein (TMEM) is a type of protein that spans biological membranes. Many of them extend through the lipid bilayer of the plasma membrane but others are located to the membrane of organelles. The TMEM family gathers proteins of mostly unknown functions. Many studies showed that TMEM expression can be down- or up-regulated in tumor tissues compared to adjacent healthy tissues. Indeed, some TMEMs such as TMEM48 or TMEM97 are defined as potential prognostic biomarkers for lung cancer. Furthermore, experimental evidence suggests that TMEM proteins can be described as tumor suppressors or oncogenes. TMEMs, such as TMEM45A and TMEM205, have also been implicated in tumor progression and invasion but also in chemoresistance. Thus, a better characterization of these proteins could help to better understand their implication in cancer and to allow the development of improved therapy strategies in the future. This review gives an overview of the implication of TMEM proteins in cancer.

Over the last decade, a growing interest in the improvement of radiation therapies has led to the development of gold-based nanomaterials as radiosensitizer. Although the radiosensitization effect was initially attributed to a dose enhancement mechanism, an increasing number of studies challenge this mechanistic hypothesis and evidence the importance of chemical and biological contributions. Despite extensive experimental validation, the debate regarding the mechanism(s) of gold nanoparticle radiosensitization is limiting its clinical translation. This article reviews the current state of knowledge by addressing how gold nanoparticles exert their radiosensitizing effects from a transdisciplinary perspective. We also discuss the current and future challenges to go towards a successful clinical translation of this promising therapeutic approach.

Despite enormous efforts that have been made in the search for novel drugs and treatments, cancer continues to be a major public health problem. Moreover, the emergence of resistance to cancer chemotherapy often prevents complete remission. Researchers have thus turned to natural products mainly from plant origin to circumvent resistance. Pectin and pH- or heat-modified pectin have demonstrated chemopreventive and antitumoral activities against some aggressive and recurrent cancers. The focus of this review is to describe how pectin and modified pectin display these activities and what are the possible underlying mechanisms. The failure of conventional chemotherapy to reduce mortality as well as serious side effects makes natural products, such as pectin-derived products, ideal candidates for exerting synergism in combination with conventional anticancer drugs.