About this Research Topic
Tertiary lymphoid structures (TLS) resemble follicles of secondary lymphoid organs and arise in chronically inflamed tissues. These structures are often accompanied by increased densities of tissue infiltrating CD8+ and CD4+ T cells, myeloid cells, memory B cells, and plasma cells. TLS are associated with robust immune responses in autoimmunity leading to disease exacerbation, as well as in models of infection promoting pathogen clearance. In cancer patients, TLS formation is a significant positive prognosticator suggesting that TLS promote anticancer immune responses. Thus, strategies to induce TLS in cancer and to inhibit them in autoimmunity are being actively pursued.
Despite their association with enhanced immunity, in some cases TLS or their cellular constituents restrain immune responses. Examples of TLS-associated suppressive cell types include FoxP3+ Tregs, which inhibit antitumor CD8+ T cells in a mouse lung cancer model, and interleukin-35 secreting plasma cells, found in the CNS in mice with experimental autoimmune encephalomyelitis. Relatively little is known about what causes TLS formation in some inflamed tissues and what factors determine whether a TLS will ultimately promote or inhibit an associated immune response.
Organ-specific cues, temporal constraints, antigen availability, and the cytokine environment are all likely to play important and differential roles in the formation of TLS that can either promote or inhibit immune responses. For example, in contrast to their suppressive function in some mouse models, TLS are almost invariably associated with favorable outcomes in human lung cancer. Also, TLS form in the pancreas in settings of both diabetes and pancreatic cancer where they appear to promote immune responses, yet B-lineage cells appear to actively inhibit antitumor T cell responses in pancreatic cancer. Therefore, emerging evidence suggests that the decision of whether TLS will promote or inhibit immunity is highly context dependent.
In this Research Topic we will focus on mechanisms of TLS induction and maintenance in an organ- and disease-specific context. We will also evaluate evidence for the role of TLS in anti-cancer immune responses, the generation of TLS with activating or suppressing properties, as well as the manipulation of TLS as a form of immunotherapy.
Despite their association with enhanced immunity, in some cases TLS or their cellular constituents restrain immune responses. Examples of TLS-associated suppressive cell types include FoxP3+ Tregs, which inhibit antitumor CD8+ T cells in a mouse lung cancer model, and interleukin-35 secreting plasma cells, found in the CNS in mice with experimental autoimmune encephalomyelitis. Relatively little is known about what causes TLS formation in some inflamed tissues and what factors determine whether a TLS will ultimately promote or inhibit an associated immune response.
Organ-specific cues, temporal constraints, antigen availability, and the cytokine environment are all likely to play important and differential roles in the formation of TLS that can either promote or inhibit immune responses. For example, in contrast to their suppressive function in some mouse models, TLS are almost invariably associated with favorable outcomes in human lung cancer. Also, TLS form in the pancreas in settings of both diabetes and pancreatic cancer where they appear to promote immune responses, yet B-lineage cells appear to actively inhibit antitumor T cell responses in pancreatic cancer. Therefore, emerging evidence suggests that the decision of whether TLS will promote or inhibit immunity is highly context dependent.
In this Research Topic we will focus on mechanisms of TLS induction and maintenance in an organ- and disease-specific context. We will also evaluate evidence for the role of TLS in anti-cancer immune responses, the generation of TLS with activating or suppressing properties, as well as the manipulation of TLS as a form of immunotherapy.
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