Provided by the disclosure are compositions and methods for modulating differentiation of regulatory T cells. In some embodiments, methods include selectively decreasing IL-23R activity and/or IL-23R expression without significantly decreasing IL-12RP activity and/or IL-12RP expression.

Provided herein are methods for ex vivo expansion of a T cells, including tumor-reactive T cells, and compositions containing such T cells. Also provided are methods for treating diseases and conditions such as cancer using compositions of the present disclosure.

The disclosure provides methods and compositions for affecting the development of antigen presenting cell (APC, e.g., a macrophage or dendritic cell). The methods include maturing an APC, promoting anti-inflammatory phenotype, promoting development of a T regulatory cell (Treg) from a naive T cell. The methods generally include exposing an APC to a tryptophan derived microbiota metabolite (TDMM), such as an anti-inflammatory or pro-mucosal TDMM, and permitting the APC to mature. In some embodiments, the conditioned APC is exposed to a naive T cell to further promote development of a T regulatory cell (Treg). In some embodiments, the TDMM is selected from the group consisting of indole, indole-3-acetate, 5-hydroxyindole, and indole-3-pyruvate.

Disclosed herein is a chimeric antigen receptor T cell therapy for treating patients having a cancer, such as a cancer having one or more solid tumors.

Innate lymphoid cells (ILCs) represent innate versions of T helper and cytotoxic T cells that differentiate from committed ILC precursors (ILCP). Still, how ILCP relate to mature tissue-resident ILCs remains unclear. ILCP that are present in the blood and all tested lymphoid and non-lymphoid human tissues were identified. Human ILCP fail to express the signature transcription factors (TF) and cytokine outputs of mature NK cells and ILCs but are epigenetically poised to do so. Human ILCP robustly generate all ILC subsets in vitro and in vivo. While human ILCP express RAR related orphan receptor C (RORC), circulating ILCP can be found in RORC-deficient patients that retain potential for EOMES.sup.+ NK cells, T-BET.sup.+ ILC1, GATA-3.sup.+ ILC2 and for IL-22.sup.+ but not for IL-17A.sup.+ ILC3. A model of tissue ILC differentiation (‘ILC-poiesis’) is proposed whereby diverse ILC subsets are generated in situ from ILCP in response to environmental stressors, inflammation and infection.

The present invention relates to a serum-free conditioned medium that solves the drawbacks mentioned in the prior art, as it does not require prior handling of the cells, and it furthermore allows starting from a large population with no additional cost. This medium favors in vitro proliferation and conservation of the pluripotency potential that allows maintaining a state that is undifferentiated with respect to the subpopulation of cancer stem cells (CSCs) and in turn does not allow survival of the differentiated cells.

Innate lymphoid cells (ILCs) represent innate versions of T helper and cytotoxic T cells that differentiate from committed ILC precursors (ILCP). Still, how ILCP relate to mature tissue-resident ILCs remains unclear. ILCP that are present in the blood and all tested lymphoid and non-lymphoid human tissues were identified. Human ILCP fail to express the signature transcription factors (TF) and cytokine outputs of mature NK cells and ILCs but are epigenetically poised to do so. Human ILCP robustly generate all ILC subsets in vitro and in vivo. While human ILCP express RAR related orphan receptor C (RORC), circulating ILCP can be found in RORC-deficient patients that retain potential for EOMES.sup.+ NK cells, T-BET.sup.+ ILC1, GATA-3.sup.+ ILC2 and for IL-22.sup.+ but not for IL-17A.sup.+ ILC3. A model of tissue ILC differentiation (‘ILC-poiesis’) is proposed whereby diverse ILC subsets are generated in situ from ILCP in response to environmental stressors, inflammation and infection.

Embodiments of the instant disclosure relate to novel compositions, methods and systems for generating ILC cells. In certain embodiments, the present disclosure provides for a composition including a hematopoietic progenitor cell expressing CD48 and at least one of a CD48 ligand, a CD48 agonist or a CD48 antagonist in order to induce production of ILC2 or ILC3 (for example, NCR.sup.+ ILC3 and LTi-ILC3) cell populations. In other certain embodiments, the present disclosure provides methods of treating one or more health condition or immune-mediated condition in a subject by administering an effective amount of a composition of ILC2 or ILC3 cells generated using methods disclosed herein.

The invention includes compositions and methods for generating and expanding therapeutic Th17 cells. The invention includes contacting T cells with a composition comprising a first agent that is capable of providing a primary activation signal to T cells and a second agent that is capable of activating ICOS on T cells in the presence of Th-17 polarizing agents.

The invention includes compositions and methods for generating and expanding therapeutic Th17 cells. The invention includes contacting T cells with a composition comprising a first agent that is capable of providing a primary activation signal to T cells and a second agent that is capable of activating ICOS on T cells in the presence of Th-17 polarizing agents.