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Tertiary lymphoid organs

Tertiary lymphoid organs (TLOs) are abnormal lymph node-like structures that form in peripheral tissues at sites of chronic inflammation, such as chronic infection, transplanted organs undergoing graft rejection, some cancers, and autoimmune and autoimmune-related diseases. TLOs are regulated differently from the normal process whereby lymphoid tissues are formed during ontogeny, being dependent on cytokines and hematopoietic cells, but still drain interstitial fluid and transport lymphocytes in response to the same chemical messengers and gradients. TLOs typically contain far fewer lymphocytes, and assume an immune role only when challenged with antigens that result in inflammation. They achieve this by importing the lymphocytes from blood and lymph. TLOs often have an active germinal center, surrounded by a network of follicular dendritic cells (FDCs).

TLOs are thought to play an important role in the immune response to cancer and to have possible implications in immunotherapy. They have been observed in a number of cancer types such as melanoma, non-small cell lung cancer and colorectal cancer (reviewed in) as well as glioma. Patients with TLOs in the vicinity of their tumors tend to have a better prognosis, although the opposite is true for certain cancers. TLOs that contain an active germinal center tend to have a better prognosis than those with TLOs without a germinal center. The reason that these patients tend to live longer is thought to be the immune response against the tumor, which is mediated by the TLOs. TLOs may also promote an anti-tumor response when patients are treated with immunotherapy. TLOs have been referred to in many different ways, including as tertiary lymphoid structures (TLS) and ectopic lymphoid structures (ELS). When associated with colorectal cancer, they are often referred to as a Crohn's-like lymphoid reaction.