Microbiota-specific T follicular helper cells drive tertiary lymphoid structures and anti-tumor immunity against colorectal cancer

Overacre-Delgoffe, Abigail; Bumgarner, Hannah J.; Cillo, Anthony R.; Burr, Ansen H.P.; Tometich, Justin T.; Bhattacharjee, Amrita; Bruno, Tullia C.; Vignali, Dario A.A.; Hand, Timothy W.

doi:10.1016/j.immuni.2021.11.003

Cited by 162 publications

(92 citation statements)

References 106 publications

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“…The identification of patients with gastric cancer suitable for immunotherapy is particularly critical in the clinical environment. We observed higher immune infiltration levels in the low-risk score group, including B-cell memory and T-cell follicular helpers, and the high-risk score group had higher infiltration levels of macrophage M2 (tumor-promoting cells) ( Xia et al, 2020 ; Overacre-Delgoffe et al, 2021 ). The results of immune function analysis also showed that high-risk score patients had active immune-related functions “type_II_IFN_response” and “parainflammation,” whereas “MHC_class_I” was more active in the low-risk score group.…”

Section: Discussionmentioning

confidence: 77%

Cellular Senescence-Related Genes: Predicting Prognosis in Gastric Cancer

et al. 2022

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Our study aimed to explore the effect of cellular senescence and to find potential therapeutic strategies for gastric cancer. Cellular senescence-related genes were acquired from the CellAge database, while gastric cancer data were obtained from GEO and TCGA databases. SMARCA4 had the highest mutation frequency (6%), and it was linked to higher overall survival (OS) and progression-free survival (PFS). The gastric cancer data in TCGA database served as a training set to construct a prognostic risk score signature, and GEO data were used as a testing set to validate the accuracy of the signature. Patients with the low-risk score group had a longer survival time, while the high-risk score group is the opposite. Patients with low-risk scores had higher immune infiltration and active immune-related pathways. The results of drug sensitivity analysis and the TIDE algorithm showed that the low-risk score group was more susceptible to chemotherapy and immunotherapy. Most patients with mutation genes had a lower risk score than the wild type. Therefore, the risk score signature with cellular senescence-related genes can predict gastric cancer prognosis and identify gastric cancer patients who are sensitive to chemotherapy and immunotherapy.

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Section: Discussionmentioning

confidence: 77%

Cellular Senescence-Related Genes: Predicting Prognosis in Gastric Cancer

et al. 2022

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“…Some characteristics of tumor associated TLS, such as the presence of mature dendritic cells, T cells and actively proliferating B cells (Ki67+) in close proximity, can be indicative of ongoing antigen specific activation. Despite very few studies have specifically associated TLS presence with tumor specific immunity (Germain et al, 2014;Kroeger et al, 2016;Overacre-Delgoffe et al, 2021), the strong prognostic value of these intratumoral lymphoid structures might indeed be related to their promoting effect on antitumor responses. Also, the predictive value of response to ICI-based immunotherapy further sustains a link between TLS and tumor specific immunity.…”

Section: Discussionmentioning

confidence: 99%

Stromal and Immune Cell Dynamics in Tumor Associated Tertiary Lymphoid Structures and Anti-Tumor Immune Responses

Rossi

Belmonte

Carnevale

et al. 2022

Front. Cell Dev. Biol.

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Tertiary lymphoid structures (TLS) are ectopic lymphoid organs that have been observed in chronic inflammatory conditions including cancer, where they are thought to exert a positive effect on prognosis. Both immune and non-immune cells participate in the genesis of TLS by establishing complex cross-talks requiring both soluble factors and cell-to-cell contact. Several immune cell types, including T follicular helper cells (Tfh), regulatory T cells (Tregs), and myeloid cells, may accumulate in TLS, possibly promoting or inhibiting their development. In this manuscript, we propose to review the available evidence regarding specific aspects of the TLS formation in solid cancers, including 1) the role of stromal cell composition and architecture in the recruitment of specific immune subpopulations and the formation of immune cell aggregates; 2) the contribution of the myeloid compartment (macrophages and neutrophils) to the development of antibody responses and the TLS formation; 3) the immunological and metabolic mechanisms dictating recruitment, expansion and plasticity of Tregs into T follicular regulatory cells, which are potentially sensitive to immunotherapeutic strategies directed to costimulatory receptors or checkpoint molecules.

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“…Intestinal TLOs form postnatally, or in response to chronic inflammation and colorectal cancer in a microbiota-dependent manner (Eberl and Lochner, 2009; Koscso et al, 2020; Overacre-Delgoffe et al, 2021). Although best known for their role in T cell-independent B cell maturation, our findings indicate that TLOs also serve as an activation hub for monocyte-derived MPs (Tsuji et al ., 2008).…”

Section: Discussionmentioning

confidence: 99%

Microbial Energy Metabolism Fuels a CSF2-dependent Intestinal Macrophage Niche within Tertiary Lymphoid Organs

Chiaranunt

Burrows

Ngai

et al. 2022

Preprint

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Maintaining intestinal macrophage (MP) heterogeneity is critical to ensure tissue homeostasis and host defense. The gut microbiota and host factors are thought to synergistically shape colonic MP development, although there remains a fundamental gap in our understanding of the details of such collaboration. Here, we report tertiary lymphoid organs (TLOs), enriched in group 3 innate lymphoid cells (ILC3s), as a microbiota-operated intestinal niche for the development of monocyte-derived MPs. ILC3-derived colony stimulating factor 2 (CSF2) serves as a developmental and functional determinant for MPs and required microbe-derived extracellular adenosine triphosphate (ATP) as a trigger. Microbial communities rich in extracellular ATP promoted MP turnover via ILC3 activity in an NLRP3-dependent fashion. Single cell RNA-sequencing of MPs revealed unique TLO-associated, CSF2-dependent MP populations critical for anti-microbial defense against enteric infection. Collectively, these findings describe a fundamental framework that constitutes an intestinal MP niche fueled by microbial energy metabolism.

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Microbiota-specific T follicular helper cells drive tertiary lymphoid structures and anti-tumor immunity against colorectal cancer

Cited by 162 publications

References 106 publications

Cellular Senescence-Related Genes: Predicting Prognosis in Gastric Cancer

Cellular Senescence-Related Genes: Predicting Prognosis in Gastric Cancer

Stromal and Immune Cell Dynamics in Tumor Associated Tertiary Lymphoid Structures and Anti-Tumor Immune Responses

Microbial Energy Metabolism Fuels a CSF2-dependent Intestinal Macrophage Niche within Tertiary Lymphoid Organs

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