Immunology and Biotherapies

Highlights

 

•Anticancer therapies alter the composition, phenotype, and function of immune cells.•The immune system is a major regulator of the success of anticancer therapy.•Immunotherapy and immunomodulatory agents often synergize with conventional therapies.•Resistance mechanisms following immunotherapy and immunodulatory agents are not fully defined.•Targeting both cancer cells and immune cells may be the key to fight metastasis.

 

Conventional anticancer therapies, such as chemotherapy, radiotherapy, and targeted therapy, are designed to kill cancer cells. However, the efficacy of anticancer therapies is not only determined by their direct effects on cancer cells but also by off-target effects within the host immune system. Cytotoxic treatment regimens elicit several changes in immune-related parameters including the composition, phenotype, and function of immune cells. Here we discuss the impact of innate and adaptive immune cells on the success of anticancer therapy. In this context we examine the opportunities to exploit host immune responses to boost tumor clearing, and highlight the challenges facing the treatment of advanced metastatic disease.

Via Krishan Maggon

MT @NatRevClinOncol A shed NKG2D ligand that promotes NK cell activation & #tumor rejection http://t.co/fjxcQRyDGS #immunotherapy #cancer

 

Abstract

 

Immune cells, including natural killer (NK) cells, recognize transformed cells and eliminate them in a process termed immunosurveillance. It is thought that tumor cells evade immunosurveillance by shedding membrane ligands that bind to the NKG2D activating receptor on NK cells and/or T cells, and desensitize these cells. In contrast, we show that in mice, shedding of MULT1, a high affinity NKG2D ligand, causes NK cell activation and tumor rejection. Recombinant soluble MULT1 stimulated tumor rejection in mice. Soluble MULT1 functions, at least in part, by competitively reversing a global desensitization of NK cells imposed by engagement of membrane NKG2D ligands on tumor-associated cells, such as myeloid cells. The results overturn conventional wisdom that soluble ligands are inhibitory, and suggest a new approach for cancer immunotherapy.

Via Krishan Maggon