The present invention provides universal donor cellular populations derived from umbilical cords possessing ability to elicit immune modulation and evoke regeneration when administered into a mammalian host. Generation of cellular products for clinical use are provided including methodologies of expansion, characterization, and means of therapeutic implementation.

ILC2 cells play a role in the pathogenesis of graft versus host disease (GvHD) and idiopathic pneumonia syndrome (IPS), both conditions associated with allogeneic stem cell transplantation. Infusion of IL-33 activated ILC2 cells into patients with ongoing GvHD or IPS, or prior to onset of GvHD or IPS in susceptible patients, substantially ameliorates the disease and improves survival.

The present invention provides methods of expanding γδ T cells from a non-haematopoietic tissue source. Further provided are compositions of expanded γδ T cells and methods of using the expanded γδ T cells (e.g., apart of an adoptive T cell therapy).

ILC2 cells play a role in the pathogenesis of graft versus host disease (GvHD) and idiopathic pneumonia syndrome (IPS), both conditions associated with allogeneic stem cell transplantation. Infusion of IL-33 activated ILC2 cells into patients with ongoing GvHD or IPS, or prior to onset of GvHD or IPS in susceptible patients, substantially ameliorates the disease and improves survival.

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 is directed to methods of inducing a phenotypic change in a population of monocytes and; or macrophages. The method includes administering to the population of monocytes and/or macrophages, a macrophage stimulating agent coupled to a carrier molecule, wherein the carrier molecule facilitates macropinocytic uptake of the agent by monocytes and macrophages in the population and is defective in neonatal Fc receptor binding, wherein the administering induces a phenotypic change in the monocytes and macrophages in the population.

The present invention provides methods of modulating of cancer immunity using type 2 innate lymphoid cells (ILC2s), interleukin 33 (IL-33), IFI44 or combination thereof. Also provided are methods of preventing tumor metastasis and/or cancer progression by treatment with therapies comprising type 2 innate lymphoid cells (ILC2s), interleukin 33 (IL-33), IFI44 or combination thereof. Also provided are diagnostic methods for assessing cancer prognosis.

The present disclosure relates to a method of improving cognitive function in a subject. The method includes implanting group-2 innate lymphoid cells (ILC2) in a cranium of a subject, where the ILC2 was treated with an ILC2 activator. The present disclosure further relates to a method including selecting a subject having aging-associated cognitive decline and administering to the subject an activator of innate lymphoid cell activity under conditions effective to promote innate lymphoid cell activity. The present disclosure further relates to a method of improving cognition in a subject. The method includes selecting a subject having aging-associated cognitive decline and administering to the subject a cytokine selected from the group consisting of IL-33, IL-5, IL-7, IL-25, and thymic stromal lymphopoietin.

The present invention provides methods of expanding γδ T cells from a non-haematopoietic tissue source. Further provided are compositions of expanded γδ T cells and methods of using the expanded γδ T cells (e.g., a part of an adoptive T cell therapy).

The present disclosure provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to an immunoresponsive cell comprising an antigen-recognizing receptor (e.g., a chimeric antigen receptor (CAR) or a T cell receptor (TCR)), and expressing increased level of IL-33. In certain embodiments, the engineered immunoresponsive cells are antigen-directed and have enhanced immune-activating properties.