Abstract: Described herein are novel compositions comprising MT1 and/or MT2 modulators (i.e., inhibitors or activators), and methods using these agents for targeting different T-cell populations, for example, type 1 regulatory (Tr1) CD4+ cells and exhausted CD8+ T-cells cells. Aspects of the invention relate to inhibitors of MT1 and/or MT2 to increase the differentiation of CD4+ cell Trl1 CD4+ cells and increase in the activity of Tr1 cells, e.g., to increase IL-10 production. In alternative embodiments, MT1 and/MT1 inhibitors can be used to increase proliferation and/or activity of exhausted CD8+ T-cells and to decrease CD8+ T-cell exhaustion (e.g., decrease functionally exhausted or unresponsive CD8+ immune cells). Accordingly, aspects of the present invention relate to compositions and methods comprising inhibitors of MT1 and/or MT2 useful in the treatment of chronic immune conditions, such as persistent infections, cancer, and autoimmune disease.

Abstract: The present invention relates to an in vitro method of assessing the sensitivity of a subject to a treatment of cancer, which method comprises detecting the presence of a mutated Toll Like Receptor 4 (TLR4) nucleic acid or an abnormal TLR4 protein expression or activity in a sample from the subject, the presence of said mutated TLR4 nucleic acid or abnormal TLR4 expression or activity being indicative of a resistance to said treatment. The invention further provides compounds for treating or preventing a cancer in a subject having a mutated TLR4 nucleic acid or an abnormal TLR4 protein expression or activity.

Abstract: The present invention concerns methods for assessing the sensibility of a subject to an anticancer treatment, for screening compounds which are useful for treating a cancer and for determining the likelihood of a metastatic relapse in a subject. The methods are based on the finding that a non-functional P2X7-elicited NALP3 inflammasome pathway in a subject is indicative of a resistance to treatment. The invention further concerns methods for treating a cancer and for restoring the sensitivity of the subject to a cancer treatment.

Abstract: The present invention relates to an in vitro method of assessing the sensitivity of a subject to a treatment of cancer, which method comprises detecting the presence of a mutated Toll Like Receptor 4 (TLR4) nucleic acid or an abnormal TLR4 protein expression or activity in a sample from the subject, the presence of said mutated TLR4 nucleic acid or abnormal TLR4 expression or activity being indicative of a resistance to said treatment. The invention further provides compounds for treating or preventing a cancer in a subject having a mutated TLR4 nucleic acid or an abnormal TLR4 protein expression or activity.