Lymphocyte networks are dynamic cellular communities in the immunoregulatory landscape of lung adenocarcinoma

Gaglia, Giorgio; Burger, M.; Ritch, Cecily C.; Rammos, Danae; Dai, Yang; Crossland, Grace E.; Tavana, Sara; Warchol, Simon; Jaeger, Alex M.; Naranjo, Santiago; Coy, Shannon; Nirmal, Ajit J.; Krueger, Robert F.; Lin, Jia-Ren; Pfister, Hanspeter; Sorger, Peter K.; Jacks, Tyler; Santagata, Sandro

doi:10.1101/2022.08.11.503237

Cited by 2 publications

(1 citation statement)

References 49 publications

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“…Accurate in vitro models of the patient specific tumor immune microenvironment (TIME) and robust analysis techniques enabling in-depth dissection of the in vitro model are indispensable for the development of next generation immunotherapy. Imaging-based and sequencing-based analysis of the surgically dissected patient tissues has enabled the deconvolution of not only the cell types that constitute the TIME but also their cellstate heterogeneity (1)(2)(3)(4) . However, they can only provide the snapshots rather than the dynamics of TIME, i.e., the subtle changes of TIME in response to treatments.…”

Section: Introductionmentioning

confidence: 99%

Function-associated scRNA-seq on single lung cancer organoids unravels the immune landscape of tumor parenchyma

Liu,

Li,

Sui

et al. 2023

Preprint

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In vitro models coupled with multimodal approaches are urgently needed to decipher the local tumor immune microenvironment (TIME) owing to the heterogeneous nature of immune cells and their diverse spatial distributions. Here we generate primary lung cancer organoids (pLCOs) by isolating the tumor cell clusters, including the infiltrated immune cells, from dissected lung cancer samples. A FascRNA-seq platform allowing both phenotypic evaluation and the scRNA-seq of all the single cells in an organoid was developed to dissect the TIME in individual pLCOs. Our analysis on 171 individual pLCOs derived from 7 patients revealed that pLCOs retained the fundamental features as well as intra-tumor heterogeneity of local TIME in the parenchyma of parental tumor tissues, providing a series of models with consistent genetic background but various TIME. Linking the single cell transcriptome data of individual pLCOs with their responses to ICB allowed us to confirm the pivotal role of CD8+Ts in ICB induced anti-tumor immunity, to identify the potential tumor-reactive T cells with a set of 10 genes, and to unravel the factors regulating T cell activity.

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Section: Introductionmentioning

confidence: 99%

Function-associated scRNA-seq on single lung cancer organoids unravels the immune landscape of tumor parenchyma

Liu,

Li,

Sui

et al. 2023

Preprint

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A multidimensional analysis reveals distinct immune phenotypes and tertiary lymphoid structure-like aggregates in the bone marrow of pediatric acute myeloid leukemia

Koedijk

Werf

Vermeulen

et al. 2023

Preprint

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Pediatric cancers are characterized by a relatively low mutational burden and therefore, children are thought to be poor candidates for T cell-engaging immunotherapies. Here, we performed a multidimensional characterization of the tumor immune microenvironment in newly diagnosed children with acute myeloid leukemia (AML) and non-leukemic controls. We identified a subset of pediatric AML patients with remarkably high levels of T cell infiltration and a relatively low abundance of anti-inflammatory macrophages. In addition, we detected large T cell networks that colocalized with B cells in the bone marrow of immune-infiltrated samples, resembling tertiary lymphoid structures as described in solid tumors. Using spatial transcriptomics, we dissected the composition of these structures and revealed unique hotspots of anti-tumor immunity. This work raises the possibility that a subset of pediatric AML patients may benefit from T cell-engaging immunotherapies and encourages further study of these lymphoid structures in the context of immunotherapy in AML.Disclosure of conflicts of interestThe authors declare no financial conflicts of interest.

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Lymphocyte networks are dynamic cellular communities in the immunoregulatory landscape of lung adenocarcinoma

Cited by 2 publications

References 49 publications

Function-associated scRNA-seq on single lung cancer organoids unravels the immune landscape of tumor parenchyma

Function-associated scRNA-seq on single lung cancer organoids unravels the immune landscape of tumor parenchyma

A multidimensional analysis reveals distinct immune phenotypes and tertiary lymphoid structure-like aggregates in the bone marrow of pediatric acute myeloid leukemia

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