About this Research Topic
Immune cell therapy is promising to alleviate the progression of non-infectious diseases including cancer, graft-versus-host disease (GVHD), organ function damage caused by acute and chronic diseases, and autoimmune diseases. Genetic and epigenetic modification of lymphocyte-derived cells, such as T cells and natural killer (NK) cells, can directly regulate immune responses. For example, anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has achieved great success in the treatment of B-cell acute lymphoblastic leukemia. Meanwhile, the infusion of regulatory T (Treg) cells was applied to prevent GVHD after stem cell transplantation. Although the engineered lymphocytes can effectively treat hematologic diseases, they are difficult to reach the focus or solid tumours directly because of the low efficiency of traffic and stromal tissue penetration. To overcome this limitation, immune cell therapy using myeloid lineage cells was developed, which participates in the establishment of inflammation and immune microenvironment by regulating antigen presentation and immune responses.
Immune cell therapy is a powerful tool in cancer treatment to avoid immune escape, rebuild immune surveillance, and enhance host immune function in tumour microenvironment (TME), while the discovery of tumour-associated antigens (TAAs) and optimization of CAR cell therapy relies on the genetic and epigenetic exploration of both cancer and immune cells. Genome-wide CRISPR screening and high-throughput sequencing facilitate the exploration of TAAs and also accelerate relevant research in CAR-T, CAR-NK, and CAR-macrophage therapy. For example, the discovery of CAR-T resistance regulators, including NOXA, RASA2, and PRDM1, provides genetic and pharmacologic targets. Meanwhile, localized cytokines and chemokines regulate the development, differentiation, and infiltration of immune cells. For example, the high level of IL-2 and IL-12 correlates with the increase and activation of innate immune cells including MHC II+ dendritic cells and M1-like macrophage in TME. This suggests the crucial role of cytokines and chemokines in immune cell regulation and treatment. As important epigenetic regulators, RNA molecules (miRNAs, lncRNAs, circRNAs) also modulate immune-related genes and cancer immunity. There are reports that miR-150 and lncRNA-GM can regulate effector T cells and regulatory T cells respectively, while circUSP7 secreted by lung cancer cells suppresses CD8+ T-cell function. Additionally, immune cell therapy is also expected to improve the treatment of other non-infectious diseases. For example, CD19 CAR-T cell was successfully used for sustained CD19+ B cell depletion and lupus treatment in mice models, while adoptive Treg cell therapy is a potential treatment for systemic lupus erythematosus. Immune cell therapy has great potential in non-infectious disease treatment. However, it also faces many difficulties and challenges including treatment toxicity, the insufficient migratory capacity of engineered immune cells, and uncontrolled cytokine release. Studies on the genetics and epigenetics of immune cells will effectively guide the clinical practice of immune cell therapy in non-infectious diseases.
This Research Topic aims to include cutting-edge research and discussions from the genetic and epigenetic perspective on the development and regulation of immune cells, antitumor immunity and vaccines, and immune cell therapy for non-infectious disease treatment. We welcome submissions of Original Research, Review articles, or Opinion papers; the topics of interest include but are not limited to the following:
• Genetic and epigenetic variation on the establishment of inflammation and immunity environment in non-infectious diseases.
• Exploration for neoantigen-encoding genes, neoantigen-loaded immune cells, and vaccines.
• Development of technology and strategy for finding novel immunogenetic and therapeutic targets.
• Effects of stem and progenitor cell function alternation and differentiation on immune responses.
• Genetical, pharmacological, and combined treatment of immune cell therapy in non-infectious diseases.
Note: In line with the section policy, submissions based purely on bioinformatics analyses, i.e. lacking experimental validation, will not be considered.
Immune cell therapy is a powerful tool in cancer treatment to avoid immune escape, rebuild immune surveillance, and enhance host immune function in tumour microenvironment (TME), while the discovery of tumour-associated antigens (TAAs) and optimization of CAR cell therapy relies on the genetic and epigenetic exploration of both cancer and immune cells. Genome-wide CRISPR screening and high-throughput sequencing facilitate the exploration of TAAs and also accelerate relevant research in CAR-T, CAR-NK, and CAR-macrophage therapy. For example, the discovery of CAR-T resistance regulators, including NOXA, RASA2, and PRDM1, provides genetic and pharmacologic targets. Meanwhile, localized cytokines and chemokines regulate the development, differentiation, and infiltration of immune cells. For example, the high level of IL-2 and IL-12 correlates with the increase and activation of innate immune cells including MHC II+ dendritic cells and M1-like macrophage in TME. This suggests the crucial role of cytokines and chemokines in immune cell regulation and treatment. As important epigenetic regulators, RNA molecules (miRNAs, lncRNAs, circRNAs) also modulate immune-related genes and cancer immunity. There are reports that miR-150 and lncRNA-GM can regulate effector T cells and regulatory T cells respectively, while circUSP7 secreted by lung cancer cells suppresses CD8+ T-cell function. Additionally, immune cell therapy is also expected to improve the treatment of other non-infectious diseases. For example, CD19 CAR-T cell was successfully used for sustained CD19+ B cell depletion and lupus treatment in mice models, while adoptive Treg cell therapy is a potential treatment for systemic lupus erythematosus. Immune cell therapy has great potential in non-infectious disease treatment. However, it also faces many difficulties and challenges including treatment toxicity, the insufficient migratory capacity of engineered immune cells, and uncontrolled cytokine release. Studies on the genetics and epigenetics of immune cells will effectively guide the clinical practice of immune cell therapy in non-infectious diseases.
This Research Topic aims to include cutting-edge research and discussions from the genetic and epigenetic perspective on the development and regulation of immune cells, antitumor immunity and vaccines, and immune cell therapy for non-infectious disease treatment. We welcome submissions of Original Research, Review articles, or Opinion papers; the topics of interest include but are not limited to the following:
• Genetic and epigenetic variation on the establishment of inflammation and immunity environment in non-infectious diseases.
• Exploration for neoantigen-encoding genes, neoantigen-loaded immune cells, and vaccines.
• Development of technology and strategy for finding novel immunogenetic and therapeutic targets.
• Effects of stem and progenitor cell function alternation and differentiation on immune responses.
• Genetical, pharmacological, and combined treatment of immune cell therapy in non-infectious diseases.
Note: In line with the section policy, submissions based purely on bioinformatics analyses, i.e. lacking experimental validation, will not be considered.
Keywords: Immune cell, Antitumor immunity, Personalized medicine, Immunogenetics, Genetics, Epigenetics, Cytokines, Cancer Vaccine
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
