Neutrophils are the protagonists of the host immune response,possessing potent antimicrobial and inflammatory capacities.The neutrophil reservoir as well as the development,mobilization,chemotaxis,pro-inflammatory act...Neutrophils are the protagonists of the host immune response,possessing potent antimicrobial and inflammatory capacities.The neutrophil reservoir as well as the development,mobilization,chemotaxis,pro-inflammatory activity,and clearance of neutrophils are strictly regulated to prevent inflammation-induced tissue damage.Inflammation pervades almost every type of cancer.However,there is growing awareness that although the tumor microenvironment has the capacity to recruit neutrophils,the functions are diverse and include roles other than that of sentinels in cancer.This review highlights the heterogeneity of neutrophils in tumors,discusses the dual role of neutrophils as angels and demons in tumorigenesis,invasion,and metastasis,and examines the potential of neutrophils as targets in clinical therapy.展开更多
Colorectal cancer has one of the highest mortality rates among malignant tumors,and most patients with non-microsatellite instability-high (MSI-H) colorectal cancer do not benefit from targeted therapy or immune check...Colorectal cancer has one of the highest mortality rates among malignant tumors,and most patients with non-microsatellite instability-high (MSI-H) colorectal cancer do not benefit from targeted therapy or immune checkpoint inhibitors.Identification of immunogenic neoantigens is a promising strategy for inducing specific antitumor T cells for cancer immunotherapy.Here,we screened potential high-frequency neoepitopes from non-MSI-H colorectal cancer and tested their abilities to induce tumorspecific cytotoxic T cell responses.Three HLA-A2-restricted neoepitopes (P31,P50,and P52) were immunogenic and could induce cytotoxic T lymphocytes in peripheral blood mononuclear cells from healthy donors and colorectal cancer patients.Cytotoxic T lymphocytes induced in HLA-A2.1/K^(b) transgenic mice could recognize and lyse mutant neoepitope-transfected HLA-A2^(+) cancer cells.Adoptive transfer of cytotoxic T lymphocytes induced by the peptide pool of these three neoepitopes effectively inhibited tumor growth and increased the therapeutic effects of anti-PD-1 antibody.These results revealed the potential of high-frequency mutation-specific peptide-based immunotherapy as a personalized treatment approach for patients with non-MSI-H colorectal cancer.The combination of adoptive T cell therapy based on these neoepitopes with immune checkpoint inhibitors,such as anti-PD-1,could provide a promising treatment strategy for non-MSI-H colorectal cancer.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82273449 and 82203663)the Zhejiang Provincial Natural Science Foundation of China(Grant No.LQ23H160013)the Medical and Health Science and Technology Project of Zhejiang Province(Grant Nos.2024KY1039 and 2024KY1250).
文摘Neutrophils are the protagonists of the host immune response,possessing potent antimicrobial and inflammatory capacities.The neutrophil reservoir as well as the development,mobilization,chemotaxis,pro-inflammatory activity,and clearance of neutrophils are strictly regulated to prevent inflammation-induced tissue damage.Inflammation pervades almost every type of cancer.However,there is growing awareness that although the tumor microenvironment has the capacity to recruit neutrophils,the functions are diverse and include roles other than that of sentinels in cancer.This review highlights the heterogeneity of neutrophils in tumors,discusses the dual role of neutrophils as angels and demons in tumorigenesis,invasion,and metastasis,and examines the potential of neutrophils as targets in clinical therapy.
基金supported by the National Natural Science Foundation of China (U20A20369, 81822043, and 81601448)the Foundation of Henan Province (19A180007)。
文摘Colorectal cancer has one of the highest mortality rates among malignant tumors,and most patients with non-microsatellite instability-high (MSI-H) colorectal cancer do not benefit from targeted therapy or immune checkpoint inhibitors.Identification of immunogenic neoantigens is a promising strategy for inducing specific antitumor T cells for cancer immunotherapy.Here,we screened potential high-frequency neoepitopes from non-MSI-H colorectal cancer and tested their abilities to induce tumorspecific cytotoxic T cell responses.Three HLA-A2-restricted neoepitopes (P31,P50,and P52) were immunogenic and could induce cytotoxic T lymphocytes in peripheral blood mononuclear cells from healthy donors and colorectal cancer patients.Cytotoxic T lymphocytes induced in HLA-A2.1/K^(b) transgenic mice could recognize and lyse mutant neoepitope-transfected HLA-A2^(+) cancer cells.Adoptive transfer of cytotoxic T lymphocytes induced by the peptide pool of these three neoepitopes effectively inhibited tumor growth and increased the therapeutic effects of anti-PD-1 antibody.These results revealed the potential of high-frequency mutation-specific peptide-based immunotherapy as a personalized treatment approach for patients with non-MSI-H colorectal cancer.The combination of adoptive T cell therapy based on these neoepitopes with immune checkpoint inhibitors,such as anti-PD-1,could provide a promising treatment strategy for non-MSI-H colorectal cancer.
