Methods for the treatment of myeloid derived suppressor cells related disorders

Abstract

The invention features methods of treating disorders related to increased levels of myeloid derived suppressor cells such as cancer or infections. The disclosure also provides methods of treating cancer including combinations of LXRβ agonists and immunotherapies such as PD1 inhibitors, PDL1 inhibitors, and adoptive T-cell transfer therapy.

1 . A method of treating cancer in a subject having an elevated level of myeloid derived suppressor cells, comprising administering an effective amount of an LXRβ agonist to the subject, wherein the effective amount is predetermined to be effective to decrease the level of the myeloid derived suppressor cells by more than 20%. 
     
     
         2 . The method of  claim 1 , wherein the myeloid derived suppressor cells are monocytic myeloid derived suppressor cells and/or granulocytic myeloid derived suppressor cells. 
     
     
         3 . The method of  claim 1 , wherein the myeloid derived suppressor cells are circulating myeloid derived suppressor cells. 
     
     
         4 . The method of  claim 1 , wherein the cancer is metastatic. 
     
     
         5 . The method of  claim 1 , wherein the cancer is a non-metastatic cell migration cancer. 
     
     
         6 . The method of  claim 1 , wherein the cancer is selected from the group consisting of breast cancer, colon cancer, renal cell cancer, lung cancer, hepatocellular carcinoma, gastric cancer, ovarian cancer, pancreatic cancer, esophageal cancer, prostate cancer, sarcoma, glioblastoma, diffuse large B-cell lymphoma, leukemia, endometrial cancer, and melanoma. 
     
     
         7 . The method of  claim 1 , wherein the cancer is endometrial cancer. 
     
     
         8 . The method of  claim 1 , wherein the cancer is non-small cell cancer. 
     
     
         9 . The method of  claim 1 , wherein the cancer is melanoma. 
     
     
         10 . The method of  claim 1 , wherein the cancer is resistant to, or has failed to respond to prior treatment with, vemurafenib, dacarbazine, interferon therapy, a CTLA-4 inhibitor, a BRAF inhibitor, a MEK inhibitor, a PD1 inhibitor, a PDL-1 inhibitor, and/or a CAR-T therapy. 
     
     
         11 . The method of  claim 1 , further comprising administering to the subject an additional anticancer therapy. 
     
     
         12 . The method of  claim 11 , wherein the additional anticancer therapy is selected from the group consisting of a chemotherapeutic or cytotoxic agent, a differentiation-inducing agent, a hormonal agent, an immunological agent, and an anti-angiogenic agent. 
     
     
         13 . The method of  claim 11 , wherein the additional anticancer therapy is selected from the group consisting of a PD1 inhibitor, a VEGF inhibitor, a VEGFR2 inhibitor, a PDL1 inhibitor, a BRAF inhibitor, a CTLA-4 inhibitor, a MEK inhibitor, CAR-T therapy, adoptive T-cell transfer therapy and an ERK inhibitor. 
     
     
         14 . The method of  claim 1 , further comprising administering to the subject an immunotherapy. 
     
     
         15 . The method of  claim 1 , further comprising administering to the subject an immunotherapy selected from the group consisting of pembrolizumab, nivolumab, and ipilimumab. 
     
     
         16 . The method of  claim 1 , further comprising administering to the subject a chemotherapy comprising carboplatin or cisplatin. 
     
     
         17 . The method of  claim 1 , The method of  claim 1 , further comprising administering to the subject a chemotherapy comprising pemetrexed. 
     
     
         18 . The method of  claim 1 , further comprising administering to the subject a chemotherapy comprising docetaxel. 
     
     
         19 . The method of  claim 1 , further comprising determining the level of the myeloid derived suppressor cells in the subject. 
     
     
         20 . The method of  claim 1 , wherein the level of the myeloid derived suppressor cells in the subject is higher than a reference by more than about 50%.