Human Leukocyte Antigen (HLA) part 80

hla protein 1

 

HLA-G,-E and -F are important regulators of the immune system, and their role in tumour immunology is attracting a steadily growing interest. The upregulation of HLA-G, -E and -F following interferon-γ stimulation suggests that non-classical HLA class I molecules may be involved  in negative feedback responses to potentially harmful pro-inflammatory responses. Inflammation is also one of the hallmarks  of cancer. While inflammatory responses  are required to eliminate cancer cells, they also trigger strong immuno-regulatory mechanisms that limit the recognition of malignant cells  by the immune system, hence favouring tumour suppression.  Thus, tumour results in the recruitment strongly immunosuppresive cells such as Tregs, myeloid-derived supressor cells and tumour infiltrating macrophages. Non-classical HLA class I molecules constitute another means whereby malignant cells escapes  immune-surveilance. Indeed, these molecules inhibit the activity of the immune system by binding to inhibitory receptors  expressed by effector cells, hence suppressing  their functions or inducing their apoptotic demise. Thus, the molecules  might become an important target for anticancer immunotherapy. Interfering with  the functions of non-classical HLA class I molecules might robustly  boost the antineoplastic  potential of cytotoxic effectors while antagonizing the activity of intrinsically immunosuppressive cells. The specific mechanisms whereby  these molecules  control excessive inflammation are currently under investigation for theurapeutic purposes, not only in the context of anticancer immunotherapy.

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