Targeting stroma to treat cancers

Engels, Boris; Rowley, Donald A.; Schreiber, Hans

doi:10.1016/j.semcancer.2011.12.008

Cited by 69 publications

(65 citation statements)

References 158 publications

(165 reference statements)

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“…It is well established that the tumor microenvironment is needed to support the growth and metastasis of tumors, and that tumor cells induce changes in the microenvironment to facilitate those processes (13)(14)(15). The stromal tissue supports the growth of tumors, orchestrating a completely new structural and molecular microenvironment.…”

Section: Introductionmentioning

confidence: 99%

RAS interaction with PI3K p110α is required for tumor-induced angiogenesis

Murillo¹,

Zelenay²,

Nye³

et al. 2014

J. Clin. Invest.

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Section: Introductionmentioning

confidence: 99%

RAS interaction with PI3K p110α is required for tumor-induced angiogenesis

Murillo¹,

Zelenay²,

Nye³

et al. 2014

J. Clin. Invest.

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“…Relapses are still uncontrolled despite the dramatic improvement in treatment responses obtained over the last decade. 1 The microenvironment is now viewed as an important player in the development of many tumors, 2 including MM. 3 APRIL, a member of the tumor necrosis factor family, is considered as a MM-promoting factor from the microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Myelopoiesis dysregulation associated to sustained APRIL production in multiple myeloma-infiltrated bone marrow

Matthes

Mckee²,

Dunand-Sauthier³

et al. 2015

Leukemia

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Multiple myeloma (MM) is a non-curable tumor developing in the bone marrow (BM). The BM microenvironment rich in hematopoietic precursors is suspected to have a role in MM development. Here we show that a proliferation-inducing ligand (APRIL) mediated in vivo MM promotion. In MM-infiltrated BM, APRIL originated from differentiating myeloid cells with an expression peak in precursor cells. Notably, APRIL expression stayed stable in BM despite MM infiltration. The pool of APRIL-producing cells changed upon MM infiltration. Although CD16(+) mature myeloid cells constituted about half of the APRIL-producing cells in healthy BM, CD16(-) Elastase(+) myeloid precursor cells were predominant in MM-infiltrated BM. Myeloid precursor cells secreted all the APRIL they produced, and binding of secreted APRIL to MM cells, strictly dependent of heparan sulfate carried by CD138, resulted in an in situ internalization by tumor cells. This indicated APRIL consumption by MM in BM. Taken together, our data show that myelopoiesis dysregulation characterized by an increased proportion of precursor cells occurs in MM patients. Such dysregulation correlates with a stable expression of the MM-promoting factor APRIL in infiltrated BM

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“…This potential clinical benefit provides a rationale for the use of LMP1-based immunotherapy for cancer treatment (6,49,50). This study also demonstrates the antigenic and angiogenic activity of the MHC-II + stromal cells, thus supporting therapies such as the emerging T cell therapy that targets tumor stroma (33,51).…”

Section: Discussionmentioning

confidence: 53%

EBV Oncogene N-LMP1 Induces CD4 T Cell–Mediated Angiogenic Blockade in the Murine Tumor Model

Wang

Liu

et al. 2015

The Journal of Immunology

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Antivascular immunity may provide long-term protection by preventing neovascularization that precedes tumor progression. Although the tumorigenesis promoted by EBV-encoded oncogene latent membrane protein 1 derived from Taiwanese nasopharyngeal carcinoma (N-LMP1) has been demonstrated, the potential of N-LMP1 for inducing immune surveillance remains elusive. In this article, we describe the immunogenicity of N-LMP1 (1510) and its induction of antivascular immunity in a transplantable tumor model in immunocompetent BALB/c mice. The immunogenicity of N-LMP1 was evaluated on the basis of tumor rejection following immunization. The impact of the immunization on the dynamics of tumor angiogenesis was assessed by temporal noninvasive dynamic contrast-enhanced magnetic resonance imaging and was further confirmed by histologic study and vascular count. Through the experiments of in vivo depletion and adoptive transfer, CD4 T cells were identified as effectors that depend on IFN-γ for tumor prevention. The response was further verified by the identification of an MHC H-2 I-Ed–restricted peptide derived from N-LMP1 and by the immunization of mice with N-LMP1 peptide–loaded dendritic cells. These studies provide insight into N-LMP1–specific immunity in vivo, which suggests that CD4 T cells may play an important role in angiogenic surveillance against LMP1–associated cancer via tumor stroma targeting.

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Targeting stroma to treat cancers

Cited by 69 publications

References 158 publications

RAS interaction with PI3K p110α is required for tumor-induced angiogenesis

RAS interaction with PI3K p110α is required for tumor-induced angiogenesis

Myelopoiesis dysregulation associated to sustained APRIL production in multiple myeloma-infiltrated bone marrow

EBV Oncogene N-LMP1 Induces CD4 T Cell–Mediated Angiogenic Blockade in the Murine Tumor Model

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