CD39+PD-1+CD8+ T cells mediate metastatic dormancy in breast cancer

Lara, Paulino Tallón de; Castañón, Héctor; Vermeer, Marijne; Núñez, Nicolás Gonzalo; Siliņa, Karīna; Sobottka, Bettina; Urdínez, Joaquín; Cecconi, Virginia; Yagita, Hideo; Attar, Farkhondeh Movahedian; Hiltbrunner, Stefanie; Glarner, Isabelle; Moch, Holger; Tugues, Sònia; Broek, Maries van den

doi:10.1038/s41467-021-21045-2

Cited by 53 publications

(48 citation statements)

References 78 publications

(14 reference statements)

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“…Nevertheless, the association of CD127− CD39 hi , but not of CD127+ CD39 lo Trm cells with improved OS and BC-specific survival in the METABRIC cohort, their increase presence at the tumor site compared to adjacent tissue and the peripheral blood, and in metastatic vs. nonmetastatic lymph nodes suggests that CD39 is a marker of bona fide tumor-reactive T cells also in BC. In line with this conclusion, a study recently published while this paper was under review mechanistically linked the infiltration of CD39 hi PD-1 hi T cells to metastatic dormancy in BC 38 . Collectively, these results thus extend a previous study in BC patients on the prognostic role of CD8+ CD103+ Trm cells as a whole 12 and pinpoint those T cells that are preferentially associated with delayed tumor growth with enhanced precision.…”

Section: Discussionsupporting

confidence: 68%

Single-cell profiling defines the prognostic benefit of CD39high tissue resident memory CD8+ T cells in luminal-like breast cancer

et al. 2021

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Luminal-like breast cancer (BC) constitutes the majority of BC subtypes, but, differently from highly aggressive triple negative BC, is poorly infiltrated by the immune system. The quality of the immune infiltrate in luminal-like BCs has been poorly studied, thereby limiting further investigation of immunotherapeutic strategies. By using high-dimensional single-cell technologies, we identify heterogeneous behavior within the tissue-resident memory CD8+ T (Trm) cells infiltrating luminal-like tumors. A subset of CD127− CD39hi Trm cells, preferentially present in the tumor compared to the adjacent normal breast tissue or peripheral blood, retains enhanced degranulation capacity compared to the CD127+ CD39lo Trm counterpart ex vivo, and is specifically associated with positive prognosis. Nevertheless, such prognostic benefit is lost in the presence of highly-suppressive CCR8hi ICOShi IRF4+ effector Tregs. Thus, combinatorial strategies aiming at boosting Trm function and infiltration while relieving from Treg-mediated immunosuppression should be investigated to achieve proper tumor control in luminal-like BCs.

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Section: Discussionsupporting

confidence: 68%

Single-cell profiling defines the prognostic benefit of CD39high tissue resident memory CD8+ T cells in luminal-like breast cancer

et al. 2021

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“…A discrete population of CD39+PD-1+CD8+ T cells mediates metastatic dormancy in breast cancer. These distinct cells are only found in primary tumors and in dormant metastasis, but they are hardly found in aggressively metastasizing tumors [ 38 ].…”

Section: Dormancy Nichementioning

confidence: 99%

Molecular and Immune Phenotypic Modifications during Metastatic Dissemination in Lung Carcinogenesis

Tsavlis

Katopodi

Anestakis

et al. 2022

Cancers

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The tumor microenvironment plays a key role in the progression of lung tumorigenesis, progression, and metastasis. Recent data reveal that disseminated tumor cells (DTCs) appear to play a key role in the development and progression of lung neoplasiaby driving immune system dysfunction and established immunosuppression, which is vital for evading the host immune response. As a consequence, in this review we will discuss the role and function of DTCs in immune cell signaling routes which trigger drug resistance and immunosuppression. We will also discuss the metabolic biology of DTCs, their dormancy, and their plasticity, which are critical for metastasis and drive lung tumor progression. Furthermore, we will consider the crosstalk between DTCs and myeloid cells in tumor-related immunosuppression. Specifically, we will investigate the molecular immune-related mechanisms in the tumor microenvironment that lead to decreased drug sensitivity and tumor relapse, along with strategies for reversing drug resistance and targeting immunosuppressive tumor networks. Deciphering these molecular mechanisms is essential for preclinical and clinical investigations in order to enhance therapeutic efficacy. Furthermore, a better understanding of these immune cell signaling pathways that drive immune surveillance, immune-driven inflammation, and tumor-related immunosuppression is necessary for future personalized therapeutic approaches.

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“…Extending our knowledge of immune cell subpopulations, their functional states, and the roles that these cells play in dormancy, recurrence, and treatment susceptibility of ER+ metastatic disease in different locations, is a critical area of need. A recent study suggested the intriguing possibility that a T cell subset may mediate tumor dormancy [112].…”

Section: Differences Between the Microenvironments Of Primary And Metastatic Er+ Tumorsmentioning

confidence: 99%

Endogenous and Therapeutic Estrogens: Maestro Conductors of the Microenvironment of ER+ Breast Cancers

Schuler

Murdoch

2021

Cancers

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Estrogen receptor alpha (ERα) marks heterogeneous breast cancers which display a repertoire of somatic genomic mutations and an immune environment that differs from other breast cancer subtypes. These cancers also exhibit distinct biological behaviors; despite an overall better prognosis than HER2+ or triple negative breast cancers, disseminated dormant cells can lead to disease recurrence decades after the initial diagnosis and treatment. Estrogen is the best studied driver of these cancers, and antagonism or reduction of estrogen activity is the cornerstone of therapeutic approaches. In addition to reducing proliferation of ERα+ cancer cells, these treatments also alter signals to multiple other target cells in the environment, including immune cell subpopulations, cancer-associated fibroblasts, and endothelial cells via several distinct estrogen receptors. In this review, we update progress in our understanding of the stromal cells populating the microenvironments of primary and metastatic ER+ tumors, the effects of estrogen on tumor and stromal cells to modulate immune activity and the extracellular matrix, and net outcomes in experimental and clinical studies. We highlight new approaches that will illuminate the unique biology of these cancers, provide the foundation for developing new treatment and prevention strategies, and reduce mortality of this disease.

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CD39+PD-1+CD8+ T cells mediate metastatic dormancy in breast cancer

Cited by 53 publications

References 78 publications

Single-cell profiling defines the prognostic benefit of CD39high tissue resident memory CD8+ T cells in luminal-like breast cancer

Single-cell profiling defines the prognostic benefit of CD39high tissue resident memory CD8+ T cells in luminal-like breast cancer

Molecular and Immune Phenotypic Modifications during Metastatic Dissemination in Lung Carcinogenesis

Endogenous and Therapeutic Estrogens: Maestro Conductors of the Microenvironment of ER+ Breast Cancers

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