Core Viewpoint - The study highlights the role of DNASE1L3-expressing dendritic cells in enhancing CD8+ T cell function and improving the efficacy of anti-PD-1/PD-L1 therapies by degrading neutrophil extracellular traps (NETs) [2][3][5]. Group 1: Research Findings - The expression of DNASE1L3 in tumor-infiltrating dendritic cells is positively correlated with better prognosis in cancer patients undergoing anti-PD-1/PD-L1 therapy [5]. - Conditional knockout of DNASE1L3 in dendritic cells leads to accelerated tumor growth and reduced efficacy of anti-PD-L1 therapy due to impaired CD8+ T cell infiltration and function [5]. - Exogenous supplementation of DNASE1L3 enhances CD8+ T cell infiltration into the tumor microenvironment, reduces T cell exhaustion, significantly inhibits tumor growth, and improves responses to anti-PD-L1 therapy [5]. Group 2: Mechanistic Insights - DNASE1L3+ dendritic cells maintain a cytotoxic CD8+ T cell hub by degrading NETs, which inhibit the spatial distribution of CD8+ T cells within tumors [5][8]. - The absence of DNASE1L3 in dendritic cells promotes tumor growth through CD8+ T cell dysfunction [5][8]. Group 3: Implications for Therapy - DNASE1L3 is identified as a promising new target for improving the effectiveness of anti-PD-1/PD-L1 therapies [8].

Core Viewpoint - The study highlights the significant impact of respiratory viral infections, such as influenza and SARS-CoV-2, on the awakening and proliferation of dormant disseminated cancer cells (DCC) in the lungs, which may lead to increased cancer-related mortality and metastasis risk [3][14][15]. Group 1: Research Findings - Influenza and SARS-CoV-2 infections can cause dormant DCC in the lungs to awaken, leading to rapid proliferation and metastasis [3][4]. - The research indicates that the presence of interleukin-6 (IL-6) is crucial for the reactivation of DCC, as its levels increase following viral infection [9][12]. - CD4+ T cells play a necessary role in maintaining the awakened state of DCC, although they are not required to initiate this process [12][14]. Group 2: Clinical Implications - The study found that cancer patients infected with SARS-CoV-2 have a significantly higher risk of cancer-related death and lung metastasis compared to those who are not infected [14][15]. - The findings suggest a potential link between respiratory infections and the recurrence of metastatic cancer, emphasizing the need for further exploration in this area [4][15]. Group 3: Mechanisms of Action - The research demonstrated that CD4+ T cells limit the ability of CD8+ T cells to control DCC growth, indicating a complex interplay between different immune cell types in the context of viral infections and cancer [12][14]. - The study also explored the role of inflammation caused by respiratory infections in influencing dormant cancer cells, which had not been a primary focus in previous research [7][8].

Core Viewpoint - The article discusses the potential of a newly identified gut bacterium, YB328, in enhancing the efficacy of immune checkpoint blockade (ICB) therapies, particularly in cancer treatment, by promoting dendritic cell maturation and CD8+ T cell activation [1][4][7]. Group 1: Research Findings - A study published in Nature identified a gut bacterium that accelerates dendritic cell maturation and migration, increasing the response of CD8+ T cells to various tumor antigens, thereby enhancing anti-tumor immunity [2]. - The research analyzed fecal samples from 50 cancer patients undergoing PD-1 blockade therapy, revealing that the YB328 strain was significantly enriched in patients who responded to the treatment [4]. - In mouse models, fecal transplants from non-responding patients supplemented with YB328 showed significantly improved anti-tumor effects of PD-1 blockade therapy, indicating YB328's potential role in enhancing cancer immunotherapy [4]. Group 2: Mechanism of Action - YB328 promotes the differentiation of CD103+ CD11b- conventional dendritic cells (cDC), which are crucial for cross-presenting antigens to CD8+ T cells [5]. - The bacterium stimulates various Toll-like receptors (TLRs), leading to the phosphorylation of S6K and STAT3, and induces the expression of IRF8, facilitating cDC differentiation [5]. - The activated cDC migrate to tumor-draining lymph nodes and the tumor microenvironment, where they activate CD8+ T cells and induce PD-1+ CD8+ T cells targeting multiple tumor antigens [5][7]. Group 3: Future Directions - The research team is collaborating with a biotechnology company to conduct human clinical trials within the next three years to test whether YB328 can improve cancer patients' responses to checkpoint inhibitors [8].