Compositions and methods for using cross-dressing to enhance anti-tumor immune responses
Provided herein are compositions and methods of use relating to a novel class of dendritic cells, referred to herein as ISG+ DC, having anti-tumor activity.
1. A method of treating a subject having a solid cancer, comprising administering, to a subject having a malignant tumor characterized as lacking or having low levels of interferon-stimulated gene signature dendritic cells (ISG+DCs), an ISG+DC inducing agent in an effective amount,
wherein said ISG+DCs are:
(a) positive for one or more markers selected from the group consisting of Cxcl10, Ifit3, Rsad2/Viperin, Ifit1, Ifit1bl1, Ifit2, Isg15, Ifit3b, Usp18, and Ifi204; and
(b) negative for one or more markers selected from the group consisting of Batf3, IRF8, XCR1, and BDCA-3.
2. The method of claim 1 , further comprising identifying the subject having a malignant tumor characterized as lacking or having low ISG+DC level.
3. The method of claim 1 , wherein ISG+DC levels are detected based on mRNA expression.
4. The method of claim 3 , wherein the mRNA expression is obtained using bulk-RNA-seq or scRNAseq.
5. The method of claim 1 , wherein ISG+DCs are detected based on protein profile.
6. The method of claim 5 , wherein the protein profile is a cell surface protein profile.
7. The method of claim 5 , wherein the protein profile is obtained using flow cytometry or CyTOF.
8. The method of claim 1 , wherein the malignant tumor is one of the following: a melanoma tumor, a skin/cutaneous melanoma tumor, a cervical squamous cell carcinoma tumor, an endocervical adenocarcinoma tumor, a liver cancer tumor, a hepatocellular carcinoma tumor, or a sarcoma tumor.
9. The method of claim 1 , wherein the ISG+DC inducing agent is dsRNA or an analog thereof.
10. The method of claim 1 , wherein the ISG+DC inducing agent is polyI:C.
11. The method of claim 1 , wherein the ISG+DC inducing agent is one or more of dsRNA or an analog thereof, polyI:C, a RIG-1 agonist, a MDA5 agonist, a MAVS pathway activator, a TLR 3 agonist, or any combination thereof.
12. The method of claim 9 , wherein the ISG+DC inducing agent is formulated with nanoparticles.
13. The method of claim 1 , wherein a combination of two or more ISG+DC inducing agents is administered to the subject.
14. The method of claim 1 , further comprising administering one or more secondary agents to the subject in an effective amount.
15. The method of claim 1 , wherein the subject is human.
16. The method of claim 1 , further comprising administering a composition comprising an peptide-MHC Class I complex.