Conserved pan-cancer microenvironment subtypes predict response to immunotherapy

Bagaev, Alexander; Kotlov, Nikita; Nomie, Krystle; Svekolkin, Viktor; Gafurov, Azamat; Isaeva, Olga I.; Osokin, Nikita; Kozlov, Ivan; Frenkel, Felix; Gancharova, Olga; Almog, Nava; Tsiper, Maria; Ataullakhanov, Ravshan; Fowler, Nathan

doi:10.1016/j.ccell.2021.04.014

Cited by 553 publications

(468 citation statements)

References 139 publications

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“…During the leukemic transition, tumor cells grow at the expanse of normal hematopoietic cells, successfully evade or suppress immune surveillance, and consequently create a bone marrow microenvironment that is immunologically dysfunctional [6]. Emerging research in solid malignancies has shown that the number and phenotype of immune cells in the TME is predictive of response to several types of immunotherapies [23][24][25][26][27][28]. For adult AML, a similar trend is observed in early phase clinical trials [29][30][31].…”

Section: Oncolytic Virusesmentioning

confidence: 79%

“…For example, T-and natural killer (NK)-cells are considered essential for effective anti-tumor immunity, while M2-macrophages and myeloidderived suppressor cells exert tumor-supporting activities in the TME [22][23][24]. The importance of the immune system can be exemplified by the prognostic and predictive value of both the number and phenotype of immune cells in the TME for both immunotherapy interventions and conventional anticancer therapies in many cancers [22][23][24][25][26][27][28]. As a result of enormous immune profiling efforts in solid malignancies, a general overview of critical players in the TME has been generated (Figure 1).…”

Section: Immune Cells In the Tmementioning

confidence: 99%

“…As only a minority of patients respond in most immunotherapy trials, many studies have focused on elucidating factors that impact the response to immunotherapy. For instance, studies in both solid and hematological cancers have shown that patients with an immune-infiltrated or 'hot' TME have a relatively high probability of response to ICIs [23][24][25][26][27]. Such an environment has been characterized by high abundance of both CD4+ and CD8+ T-cells, opposed to low T-cell abundance in an immune-depleted or 'cold' TME.…”

Section: Figurementioning

confidence: 99%

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Paving the Way for Immunotherapy in Pediatric Acute Myeloid Leukemia: Current Knowledge and the Way Forward

Koedijk

Werf

Calkoen

et al. 2021

Cancers

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Immunotherapeutic agents may be an attractive option to further improve outcomes and to reduce treatment-related toxicity for pediatric AML. While improvements in outcome have been observed with immunotherapy in many cancer types, immunotherapy development and implementation into patient care for both adult and pediatric AML has been hampered by an incomplete understanding of the bone marrow environment and a paucity of tumor-specific antigens. Since only a minority of patients respond in most immunotherapy trials across different cancer types, it will be crucial to understand which children with AML are likely to respond to or may benefit from immunotherapies. Immune cell profiling efforts hold promise to answer this question, as illustrated by the development of predictive scores in solid cancers. Such information on the number and phenotype of immune cells during current treatment regimens will be pivotal to generate hypotheses on how and when to intervene with immunotherapy in pediatric AML. In this review, we discuss the current understanding of the number and phenotype of immune cells in the bone marrow in pediatric AML, ongoing immunotherapy trials and how comprehensive immune profiling efforts may pave the way for successful clinical trials (and, ultimately, implementation into patient care).

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Section: Oncolytic Virusesmentioning

confidence: 79%

Section: Immune Cells In the Tmementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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Paving the Way for Immunotherapy in Pediatric Acute Myeloid Leukemia: Current Knowledge and the Way Forward

Koedijk

Werf

Calkoen

et al. 2021

Cancers

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“…Most recently, pan-cancer transcriptome analyses revealed four conserved subtypes of the tumor microenvironment that correlate with response to immunotherapy [89]: immuneenriched, fibrotic (IE/F); immune-enriched, non-fibrotic (IE); fibrotic (F); and immunedepleted (D). Higher expression of genes related to angiogenesis, fibroblast and matrix remodeling was found in the IE/F and F subtypes and was associated with TGF-β signaling activation.…”

Section: Future Perspectivesmentioning

confidence: 99%

“…Interestingly, tumor mutation burden was relatively low in the IE/F and F subtypes whereas T cell infiltration was high in the IE/F subtype but was low in the F subtype. The F subtype showed inferior prognosis across various cancer types and the worst response to ICIs, indicating the need for novel cancer therapeutics targeting fibroblasts and tissue fibrosis [89].…”

Section: Future Perspectivesmentioning

confidence: 99%

Organ Specificity and Heterogeneity of Cancer-Associated Fibroblasts in Colorectal Cancer

Miyashita

Saito

2021

IJMS

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Fibroblasts constitute a ubiquitous mesenchymal cell type and produce the extracellular matrix (ECM) of connective tissue, thereby providing the structural basis of various organs. Fibroblasts display differential transcriptional patterns unique to the organ of their origin and they can be activated by common stimuli such as transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF) signaling. Cancer-associated fibroblasts (CAFs) reside in the cancer tissue and contribute to cancer progression by influencing cancer cell growth, invasion, angiogenesis and tumor immunity. CAFs impact on the tumor microenvironment by remodeling the ECM and secreting soluble factors such as chemokines and growth factors. Differential expression patterns of molecular markers suggest heterogeneous features of CAFs in terms of their function, pathogenic role and cellular origin. Recent studies elucidated the bimodal action of CAFs on cancer progression and suggest a subgroup of CAFs with tumor-suppressive effects. This review attempts to describe cellular features of colorectal CAFs with an emphasis on their heterogeneity and functional diversity.

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Integrative analysis of immune‐related multi‐omics profiles identifies distinct prognosis and tumor microenvironment patterns in osteosarcoma

Shi

et al. 2022

Molecular Oncology

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Osteosarcoma (OS) is the most common primary malignancy of bone. Epigenetic regulation plays a pivotal role in cancer development in various aspects, including immune response. In this study, we studied the potential association of alterations in the DNA methylation and transcription of immune‐related genes with changes in the tumor microenvironment (TME) and tumor prognosis of OS. We obtained multi‐omics data for OS patients from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. By referring to curated immune signatures and using a consensus clustering method, we categorized patients based on immune‐related DNA methylation patterns (IMPs), and evaluated prognosis and TME characteristics of the resulting patient subgroups. Subsequently, we used a machine‐learning approach to construct an IMP‐associated prognostic risk model incorporating the expression of a six‐gene signature ( MYC , COL13A1 , UHRF2 , MT1A , ACTB , and GBP1 ), which was then validated in an independent patient cohort. Furthermore, we evaluated TME patterns, transcriptional variation in biological pathways, somatic copy number alteration, anticancer drug sensitivity, and potential responsiveness to immune checkpoint inhibitor therapy with regard to our IMP‐associated signature scoring model. By integrative IMP and transcriptomic analysis, we uncovered distinct prognosis and TME patterns in OS. Finally, we constructed a classifying model, which may aid in prognosis prediction and provide a potential rationale for targeted‐ and immune checkpoint inhibitor therapy in OS.

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Conserved pan-cancer microenvironment subtypes predict response to immunotherapy

Cited by 553 publications

References 139 publications

Paving the Way for Immunotherapy in Pediatric Acute Myeloid Leukemia: Current Knowledge and the Way Forward

Paving the Way for Immunotherapy in Pediatric Acute Myeloid Leukemia: Current Knowledge and the Way Forward

Organ Specificity and Heterogeneity of Cancer-Associated Fibroblasts in Colorectal Cancer

Integrative analysis of immune‐related multi‐omics profiles identifies distinct prognosis and tumor microenvironment patterns in osteosarcoma

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