Abstract: As disclosed herein, stromal cells are important for the recruitment and organization of lymphocytes in TLSs. Therefore, disclosed herein are composition and methods for bioengineering TLSs in animals, such as mice. These compositions involve chemokine-releasing microparticles or cells that can be implanted into the animals. Therefore, disclosed herein are chitosan hydrogels with chemokine-releasing microparticles or cells.

Abstract: Disclosed herein is a method for enhancing antitumor T cell responses in subjects. The method involves administering to the subject in need thereof a composition comprising a demethylating agent in an amount effective to demethylate STING proteins in the tumor cells. This method is particularly useful in subjects with deficient STING expression in the tumor cells. Therefore, also disclosed is a method for treating a tumor in a subject that involves detecting in a biopsy sample from the subject reduced STING expression, reduced cGAS expression, or a combination thereof; and then administering to the subject a demethylating agent in an amount effective to demethylate STING proteins in the tumor cells. The method can further involve administering to the subject a therapeutically effective amount of a STING agonist. The method can further involve administering to the subject tumor infiltrating lymphocytes (TILs), such as HLA-matched TILs.

Abstract: Disclosed herein is a method for enhancing antitumor T cell responses in subjects. The method involves administering to the subject in need thereof a composition comprising a demethylating agent in an amount effective to demethylate STING proteins in the tumor cells. This method is particularly useful in subjects with deficient STING expression in the tumor cells. Therefore, also disclosed is a method for treating a tumor in a subject that involves detecting in a biopsy sample from the subject reduced STING expression, reduced cGAS expression, or a combination thereof; and then administering to the subject a demethylating agent in an amount effective to demethylate STING proteins in the tumor cells. The method can further involve administering to the subject a therapeutically effective amount of a STING agonist. The method can further involve administering to the subject tumor infiltrating lymphocytes (TILs), such as HLA-matched TILs.

Abstract: Disclosed are combination therapies comprising an anti-macrophage receptor with collagenous structure (MARCO) antibody and an immune checkpoint inhibitor and methods of using the same to treat cancer.

Abstract: As disclosed herein, stromal cells are important for the recruitment and organization of lymphocytes in TLSs. Therefore, disclosed herein are composition and methods for bioengineering TLSs in animals, such as mice. These compositions involve chemokine-releasing microparticles or cells that can be implanted into the animals. Therefore, disclosed herein are chitosan hydrogels with chemokine releasing microparticles or cells.

Abstract: Disclosed are compositions and methods for targeted treatment of infections and cancers expressing cancers. In particular, tumor infiltrating lymphocytes (TILs) are genetically engineered to express chimeric antigen receptor (CAR) polypeptides to produce CAR-TILs that can be used with adoptive cell transfer to target, penetrate, and kill solid tumor masses. Therefore, also disclosed are methods of providing an immunotherapy in a subject with an infection or cancer that involves adoptive transfer of the disclosed CAR-TILs.

Abstract: Disclosed herein is a method for predicting the responsiveness of a subject to CD40 agonist therapy, such as agonist anti-CD40 therapy, that involves assaying a tumor sample from the subject for a 12 Chemokine gene signature demonstrating that the tumor comprises tertiary lymphoid structures containing B cells. Therefore, also disclosed herein is a method of treating tumors, such as solid tumors, in a subject that involves administering to the subject an effective amount of a composition comprising assaying a tumor sample from the subject for a 12 Chemokine gene signature demonstrating that the tumor comprises tertiary lymphoid structures (TLS) containing B cells, and treating the subject with CD40 agonist therapy, such an agonist anti-CD40 antibody.

Abstract: Disclosed herein is a method for enhancing antitumor T cell responses in subjects. The method involves administering to the subject in need thereof a composition comprising a demethylating agent in an amount effective to demethylate STING proteins in the tumor cells. This method is particularly useful in subjects with deficient STING expression in the tumor cells. Therefore, also disclosed is a method for treating a tumor in a subject that involves detecting in a biopsy sample from the subject reduced STING expression, reduced cGAS expression, or a combination thereof; and then administering to the subject a demethylating agent in an amount effective to demethylate STING proteins in the tumor cells. The method can further involve administering to the subject a therapeutically effective amount of a STING agonist. The method can further involve administering to the subject tumor infiltrating lymphocytes (TILs), such as HLA-matched TILs.

Abstract: Disclosed are compositions and methods for targeted treatment of infections and cancers expressing cancers. In particular, tumor infiltrating lymphocytes (TILs) a genetically engineered to express chimeric antigen receptor (CAR) polypeptides to produce CAR-TILs that can be used with adoptive cell transfer to target, penetrate, and kill solid tumor masses. Therefore, also disclosed are methods of providing an immunotherapy in a subject with an infection or cancer that involves adoptive transfer of the disclosed CAR-TILs.

Abstract: As disclosed herein, stromal cells are important for the recruitment and organization of lymphocytes in TLSs. Therefore, disclosed herein are composition and methods for bioengineering TLSs in animals, such as mice. These compositions involve chemokine-releasing microparticles or cells that can be implanted into the animals. Therefore, disclosed herein are chitosan hydrogels with chemokine releasing microparticles or cells.

Abstract: Disclosed herein is a method for enhancing antitumor T cell responses in subjects. The method involves administering to the subject in need thereof a composition comprising a demethylating agent in an amount effective to demethylate STING proteins in the tumor cells. This method is particularly useful in subjects with deficient STING expression in the tumor cells. Therefore, also disclosed is a method for treating a tumor in a subject that involves detecting in a biopsy sample from the subject reduced STING expression, reduced cGAS expression, or a combination thereof; and then administering to the subject a demethylating agent in an amount effective to demethylate STING proteins in the tumor cells. The method can further involve administering to the subject a therapeutically effective amount of a STING agonist. The method can further involve administering to the subject tumor infiltrating lymphocytes (TILs), such as HLA-matched TILs.