Single-cell dissection of cellular components and interactions shaping the tumor immune phenotypes in ovarian cancer

Hornburg, Milena; Desbois, Mélanie; Lu, Shan; Guan, Yinghui; Lo, Amy A.; Kaufman, Susan; Elrod, Ashley; Lotstein, Alina; DesRochers, Teresa M.; Muñoz-Rodríguez, José L.; Wang, Xingwei; Giltnane, Jennifer M.; Mayba, Oleg; Turley, Shannon J.; Bourgon, Richard; Daemen, Anneleen; Wang, Yulei

doi:10.1016/j.ccell.2021.04.004

Cited by 201 publications

(234 citation statements)

References 78 publications

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“…Despite the context-dependent variability, two recurrent subpopulations that have now been identified in several tumour entities are inflammatory CAFs (iCAFs) and myofibroblasts (myCAFs). Very briefly, these subpopulations are functionally characterised by the secretion of inflammatory cytokines and cytoskeleton remodelling, respectively [ 38 , 40 , 46 , 48 , 49 , 50 ]. In addition to different transcriptional profiles, these subpopulations were shown to be located in distinct areas of the tumour, with myCAFs being found in closer proximity to malignant cells and iCAFs localising distally [ 38 ].…”

Section: Fibroblastsmentioning

confidence: 99%

Cancer-Associated Fibroblasts: Implications for Cancer Therapy

Maia

Wiemann

2021

Cancers

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Tumour cells do not exist as an isolated entity. Instead, they are surrounded by and closely interact with cells of the environment they are emerged in. The tumour microenvironment (TME) is not static and several factors, including cancer cells and therapies, have been described to modulate several of its components. Fibroblasts are key elements of the TME with the capacity to influence tumour progression, invasion and response to therapy, which makes them attractive targets in cancer treatment. In this review, we focus on fibroblasts and their numerous roles in the TME with a special attention to recent findings describing their heterogeneity and role in therapy response. Furthermore, we explore how different therapies can impact these cells and their communication with cancer cells. Finally, we highlight potential strategies targeting this cell type that can be employed for improving patient outcome.

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Section: Fibroblastsmentioning

confidence: 99%

Cancer-Associated Fibroblasts: Implications for Cancer Therapy

Maia

Wiemann

2021

Cancers

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“…ScRNA-seq has been used in a variety of tumor research, including OvCa (1). However, most of the single-cell studies focused on OvCa cells and malignant ascites, and just one study revealed the tumor immune phenotypes of OvCa (158)(159)(160). It is believed that there will be single cell research on immune cells of ovarian cancer in the near future, which will further reveal the causes of phenotypic changes of immune cells, and provide novel gene targets to pursue as well as promising gene-based biomarkers to stratify patients for clinical actions.…”

Section: Discussionmentioning

confidence: 99%

Shaping Immune Responses in the Tumor Microenvironment of Ovarian Cancer

Luo

et al. 2021

Front. Immunol.

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Reciprocal signaling between immune cells and ovarian cancer cells in the tumor microenvironment can alter immune responses and regulate disease progression. These signaling events are regulated by multiple factors, including genetic and epigenetic alterations in both the ovarian cancer cells and immune cells, as well as cytokine pathways. Multiple immune cell types are recruited to the ovarian cancer tumor microenvironment, and new insights about the complexity of their interactions have emerged in recent years. The growing understanding of immune cell function in the ovarian cancer tumor microenvironment has important implications for biomarker discovery and therapeutic development. This review aims to describe the factors that shape the phenotypes of immune cells in the tumor microenvironment of ovarian cancer and how these changes impact disease progression and therapy.

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“…[35][36][37] It has been reported that the TMEs can be clustered into three groups: immune-desert type that lacks lymphocyte Open access infiltration, innate immune-inactivated type that infiltrated with inactivated innate immune cells and immuneinflamed type that infiltrated with high numbers of innate and adaptive immune cells. 38 Only the immune-inflamed type TME is predicted to benefit from ICI therapies, 38 which limits the efficacy of ICIs for TNBC patients. Strategies for activating tumor antigen-specific T cells might enhance the immunotherapy efficacy for advanced or metastatic TNBC.…”

Section: Discussionmentioning

confidence: 99%

Bispecific antibody targeting TROP2xCD3 suppresses tumor growth of triple negative breast cancer

Liu

Bai

Huang

et al. 2021

J Immunother Cancer

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BackgroundTriple negative breast cancer (TNBC) is a subtype of breast cancers with poor prognosis and targeted drug therapies are limited. To develop novel and efficacious therapies for TNBC, we developed a bispecific antibody F7AK3 that recognizes both trophoblast cell surface antigen 2 (TROP2) and CD3 and evaluated its antitumor activities both in vitro and in vivo.MethodsThe binding affinities of F7AK3 to the two targets, TROP2 and CD3, were evaluated by surface plasmon resonance. Binding of F7AK3 to TNBC cells and T cells were evaluated by flow cytometry. Immunofluorescent staining was performed to demonstrate the interactions between T cells with TNBC cells. The cytotoxicity of T cells against TNBC cell lines and primary tumor cells mediated by F7AK3 were determined in vitro. In vivo antitumor activity of F7AK3 was investigated in a xenograft TNBC tumor model, using immunodeficient mice that were reconstituted with human peripheral blood mononuclear cells.ResultsWe demonstrated that F7AK3 binds specifically to human TROP2 and CD3 antigens, as well as TNBC cell lines and primary tumor cells. Human T cells can only be activated by F7AK3 in the presence of target tumor cells. F7AK3 recruits T cells to TROP2+ tumor cells in vitro and into tumor tissues in vivo. Antitumor growth activity of F7AK3 is observed in a xenograft TNBC tumor model.ConclusionThis study showed the antitumor potential of an anti-TROP2xCD3 bispecific antibody F7AK3 to TNBC tumor cells both in vitro and in vivo. These data demonstrate that F7AK3 has the potential to treat TNBC patients, which warrants further preclinical and clinical evaluation of the F7AK3 in advanced or metastatic TNBC patients.

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Single-cell dissection of cellular components and interactions shaping the tumor immune phenotypes in ovarian cancer

Cited by 201 publications

References 78 publications

Cancer-Associated Fibroblasts: Implications for Cancer Therapy

Cancer-Associated Fibroblasts: Implications for Cancer Therapy

Shaping Immune Responses in the Tumor Microenvironment of Ovarian Cancer

Bispecific antibody targeting TROP2xCD3 suppresses tumor growth of triple negative breast cancer

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