The Remarkable Plasticity of Macrophages: A Chance to Fight Cancer

Abstract

It is well established that tumor-associated macrophages (TAM) found in most advanced tumors have a pro-tumoral role. In this context, TAM limit the activity of tumor-infiltrating lymphocytes (TIL), and a number of mechanisms have been described including a trapping in the stroma, impeding TIL to reach malignant cells. Based on these results, a number of therapeutic approaches have been designed to deplete TAM. However, during tumor regression induced by immunotherapeutic treatments, recent studies revealed that TAM can switch from pro-tumoral to anti-tumoral and actively cooperate with TIL. Here, we will review the two faces of TAM in their interaction with TIL. We will summarize how they can inhibit T cell activities in growing tumors, and how they may also, together with T cells, successfully contribute to tumor eradication after an appropriate stimulation. Finally, we will discuss current promising therapies combining TAM reprogramming with T cell-based immunotherapy.

The impact of PARPs and ADP-ribosylation on inflammation and host–pathogen interactions

“…The balance of the number of different immune cell types and their activation levels is crucial for health and disease. Overwhelming evidence has associated chronic inflammation with various pathological conditions and their potential causes, including atherosclerosis, cardiovascular events, cancer, autoimmune diseases, metabolic disorders, neurological diseases, and aging (Johnston et al 1987;Gisterå and Hansson 2017;Tabas and Lichtman 2017;de Vries and Quax 2018;Gomez et al 2018;Aday and Ridker 2019;Bercovici et al 2019;Di Benedetto et al 2019;Guner and Kim 2019;Horwitz et al 2019;O'Rourke et al 2019;Othman et al 2019;Trott and Fadel 2019). Many investigations have focused on the major role of macrophages in such contexts and mechanisms for their proinflammatory activation (Murray and Wynn 2011;Wynn and Vannella 2016;Gisterå and Hansson 2017;Tabas and Lichtman 2017;Decano and Aikawa 2018;Funes et al 2018;Swirski and Nahrendorf 2018;O'Rourke et al 2019).…”

CLEC3B as a potential diagnostic and prognostic biomarker in lung cancer and association with the immune microenvironment

“…However, the role of macrophage infiltration and activation in lung cancer remains controversial [43]. Generally, TAMs play a pro-tumoral role; however, they could have the capacity to cooperate with T cells in anti-tumoral action under appropriate stimulation [44]. According to the latest report, high levels of M1, CD204 + M2, and macrophages infiltration are independent factors of favorable prognosis in stage I to III NSCLC patients [45].…”

Extracellular Vesicles and Tumor-Immune Escape: Biological Functions and Clinical Perspectives

“…Cancer cells escape the control of the immune system [102] through several mechanisms; these include (i) the expression by tumor cells of "corrupted" versions of self molecules, (ii) the release of immunosuppressive substances and (iii) the aberrant expression of lymphocytes inhibitory receptor ligands. In addition, tumor cells can trigger an anti-tumor immune response by modulating macrophage functions [103]. Data in the literature showed that during the initial stages of tumorigenesis, immunosuppressive cytokines may promote anti-tumor responses; but, after long periods, they can promote cancer progression [104].…”