Antibodies(Abs)are glycoprotein molecules that represent an essential component of the adaptative immune response.They are secreted in body fluids and act as a critical part of immune defense.Although recognition of s...Antibodies(Abs)are glycoprotein molecules that represent an essential component of the adaptative immune response.They are secreted in body fluids and act as a critical part of immune defense.Although recognition of self-antigens by Abs is normally selected against during B-cell development,autoreactive Abs can be generated as a result of pathological immune responses,as observed in autoimmune diseases.Autoantibodies can also be produced in cancer patients,where they may have beneficial roles[1].Indeed,the presence of intratumoral antibody-secreting cells(ASCs)and B-cell-rich tertiary lymphoid structures(TLSs)has been observed in many cancer types and generally correlates with a favorable clinical prognosis[2,3,4,5,6].The existence of specific antitumor antibody responses suggests that tumor cells express molecules that are recognized as nonself antigens by the immune system or that tolerance of self-antigens expressed on cancer cells is lost[1,4].The study of the origin of tumor-reactive Abs and their specificity and functions is of paramount importance for understanding the development of adaptive antitumor immune responses and for revealing novel therapeutic avenues.A recent publication in Cell by Mazor et al.[7]has provided an important advance in our understanding of antibody responses in cancer.In particular,this work paves the way for the distinction between antibody-reactive tumors and antibody-nonreactive tumors,which is reminiscent of the dichotomy of the noninfiltrated“cold”tumor microenvironment(TME)in contrast with the highly infiltrated with immune cells“hot”TME[8].Moreover,an important finding of the study was the demonstration that tumor-directed autoreactivity may be either preexisting or induced by somatic hypermutations,a mechanism related to the chronicity of cancer.展开更多
基金supported by the Institut National de la Santé et de la Recherche Médicale (INSERM, France).
文摘Antibodies(Abs)are glycoprotein molecules that represent an essential component of the adaptative immune response.They are secreted in body fluids and act as a critical part of immune defense.Although recognition of self-antigens by Abs is normally selected against during B-cell development,autoreactive Abs can be generated as a result of pathological immune responses,as observed in autoimmune diseases.Autoantibodies can also be produced in cancer patients,where they may have beneficial roles[1].Indeed,the presence of intratumoral antibody-secreting cells(ASCs)and B-cell-rich tertiary lymphoid structures(TLSs)has been observed in many cancer types and generally correlates with a favorable clinical prognosis[2,3,4,5,6].The existence of specific antitumor antibody responses suggests that tumor cells express molecules that are recognized as nonself antigens by the immune system or that tolerance of self-antigens expressed on cancer cells is lost[1,4].The study of the origin of tumor-reactive Abs and their specificity and functions is of paramount importance for understanding the development of adaptive antitumor immune responses and for revealing novel therapeutic avenues.A recent publication in Cell by Mazor et al.[7]has provided an important advance in our understanding of antibody responses in cancer.In particular,this work paves the way for the distinction between antibody-reactive tumors and antibody-nonreactive tumors,which is reminiscent of the dichotomy of the noninfiltrated“cold”tumor microenvironment(TME)in contrast with the highly infiltrated with immune cells“hot”TME[8].Moreover,an important finding of the study was the demonstration that tumor-directed autoreactivity may be either preexisting or induced by somatic hypermutations,a mechanism related to the chronicity of cancer.
