Dendritic cell maturation in the tumor microenvironment

Maturation is essential for dendritic cells(DCs)to function as a bridge between innate and adaptive immunity.The plastic maturation states correspond to the multifaceted roles of DCs in the initiation of protective,tolerogenic and pathogenic immune responses.The formation of a distinct maturation state of DCs involves the complex crosstalk between the intrinsic differences in their ontogeny and the immune environments.Recent studies have defined a universal mature DC population in the tumor microenvironment(TME),but their ontogenesis and functions remain unclear.Here,we summarize recent advances in DC maturation and attempt to dissect the complex functions of mature DCs in the TME.We highlighted that there is a distinct similarity and heterogeneity of mature DCs in the TME,in which the environment and development are both important.These help us revisit the diversity of DC maturation and to better dissect the complex functions of DCs in the TME.

Lymphotoxin signalling in tertiary lymphoid structures and immunotherapy

Tertiary lymphoid structures(TLS)often develop at sites of persistent inflammation,including cancers and autoimmune diseases.In most cases,the presence of TLS correlates with active immune responses.Because of their proximity to pathological loci,TLS are an intriguing target for the manipulation of immune responses.For several years,it has become clear that lymphotoxin(LT)signalling plays critical roles in lymphoid tissue organogenesis and maintenance.In the current review,we will discuss the role of LT signalling in the development of TLS.With a focus on cancers and autoimmune diseases,we will highlight the correlations between TLS and disease progression.We will also discuss the current efforts and potential directions for manipulating TLS for immunotherapies.

Type 3 innate lymphoid cell-derived lymphotoxin prevents microbiota-dependent inflammation

Splenomegaly is a well-known phenomenon typically associated with inflammation.However,the underlying cause of this phenotype has not been well characterized.Furthermore,the splenomegaly phenotype seen in lymphotoxin(LT)signaling-deficient mice is characterized by increased numbers of splenocytes and splenic neutrophils.Splenomegaly,as well as the related phenotype of increased lymphocyte counts in non-lymphoid tissues,is thought to result from the absence of secondary lymphoid tissues in LT-deficient mice.We now present evidence that mice deficient in LTα1β2 or LTβR develop splenomegaly and increased numbers of lymphocytes in non-lymphoid tissues in a microbiota-dependent manner.Antibiotic administration to LTα1β2-or LTβR-deficient mice reduces splenomegaly.Furthermore,re-derived germ-free Ltbr−/−mice do not exhibit splenomegaly or increased inflammation in non-lymphoid tissues compared to specific pathogen-free Ltbr−/−mice.By using various LTβ-and LTβR-conditional knockout mice,we demonstrate that retinoic acid-related orphan receptorγT-positive type 3 innate lymphoid cells provide the required active LT signaling to prevent the development of splenomegaly.Thus,this study demonstrates the importance of LT-mediated immune responses for the prevention of splenomegaly and systemic inflammation induced by microbiota.