Spontaneous immune responses against glioma-associated antigens in a long term survivor with malignant glioma

Ueda, Ryo; Low, Keri L.; Zhu, Xinmei; Fujita, Mitsugu; Sasaki, Kotaro; Whiteside, Theresa L.; Butterfield, Lisa H.; Okada, Hideho

doi:10.1186/1479-5876-5-68

Cited by 29 publications

(17 citation statements)

References 31 publications

(36 reference statements)

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“…4,7 In addition to the CTA and the MDA, other glioma-associated antigens including interleukin-13 receptor (IL-13R)a2, EphA2, and survivin are being explored as suitable targets for developing vaccine strategies in glioma. [63][64][65] We have demonstrated the lack of expression of 11 CTA in all nine normal brain samples tested by RT-PCR. These observations are consistent with the restricted expression profile of CTA to the germ cells in testis and fetal ovary and trophoblast cells in normal tissue.…”

Section: Discussionmentioning

confidence: 94%

Cancer-testis and melanocyte-differentiation antigen expression in malignant glioma and meningioma

Syed¹,

Mandigo²,

Killory³

et al. 2012

Journal of Clinical Neuroscience

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Section: Discussionmentioning

confidence: 94%

Cancer-testis and melanocyte-differentiation antigen expression in malignant glioma and meningioma

Syed¹,

Mandigo²,

Killory³

et al. 2012

Journal of Clinical Neuroscience

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“…Further, they suggest that the role of infiltrating T-cells in gliomas may be critical for the design of future immunotherapies 5,17. Therefore, we investigated CD3 T-cell infiltrate in astrocytic tumors of all grades.…”

Section: Discussionmentioning

confidence: 99%

Perspectives on the immunologic microenvironment of astrocytomas

Hewedi¹,

Radwan²,

Shash³

et al. 2013

CMAR

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BackgroundThe microenvironment of astrocytomas includes infiltrative inflammatory cells that are dynamic in nature, possibly reflecting tumor biology. We evaluated the inflammatory cell infiltrate in astrocytic tumors aiming for a better understanding of their immunobiology.MethodsImmunohistochemical expression of CD68, CD3, and CD20 was investigated in 21 glioblastomas, 21 anaplastic astrocytomas, 13 diffuse astrocytomas, and 18 pilocytic astrocytomas. The inflammatory infiltrate was classified based on microanatomic location as perivascular and intratumoral, and subsequently graded semiquantitatively.ResultsPerivascularly, CD68-positive infiltrate was noted in 71.4% of glioblastomas compared with 14.3% of anaplastic astrocytomas (P = 0.0001), 7.7% of diffuse astrocytomas (P = 0.0001), and 33.3% of pilocytic astrocytomas (P = 0.017). Intratumorally, 85.7% of glioblastomas exhibited CD68-positive infiltrate compared with 42.9% of anaplastic astrocytomas (P = 0.004), 38.5% of diffuse astrocytomas (P = 0.008), and 33.3% of pilocytic astrocytomas (P = 0.001). Among diffusely infiltrating astrocytomas, intratumoral CD3-positive infiltrate was only associated with glioblastoma. A CD20-positive infiltrate was only detected in the perivascular space of a single case of diffuse astrocytoma.ConclusionThese data indicate a distinct immune profile in the glioblastoma microenvironment primarily related to the prevalence of macrophages. Thus, novel glioblastoma therapies should address this key CD68-positive population and its possible role in generating an antitumor immune response.

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“…Despite all these hurdles for T-lymphocytes to reach the tumor site, many investigators have observed the presence of glioma T-cell infiltrates in patient tissues, implying the generation of spontaneous antitumor immune responses (23). Whether these T-cell responses in therapy-naive patients are linked to their clinical outcome is still not clear.…”

Section: Introductionmentioning

confidence: 99%

Effector T-Cell Infiltration Positively Impacts Survival of Glioblastoma Patients and Is Impaired by Tumor-Derived TGF-β

Lohr

Ratliff

Huppertz

et al. 2011

Clinical Cancer Research

293

251

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Purpose: In glioma-in contrast to various other cancers-the impact of T-lymphocytes on clinical outcome is not clear. We investigated the clinical relevance and regulation of T-cell infiltration in glioma.Experimental Design: T-cell subpopulations from entire sections of 93 WHO II-IV gliomas were computationally identified using markers CD3, CD8, and Foxp3; survival analysis was then done on primary glioblastomas (pGBM). Endothelial cells expressing cellular adhesion molecules (CAM) were similarly computationally quantified from the same glioma tissues. Influence of prominent cytokines (as measured by ELISA from 53 WHO II-IV glioma lysates) on CAM-expression in GBM-isolated endothelial cells was determined using flow cytometry. The functional relevance of the cytokine-mediated CAM regulation was tested in a transmigration assay using GBM-derived endothelial cells and autologous T-cells.Results: Infiltration of all T-cell subsets increased in high-grade tumors. Most strikingly, within pGBM, elevated numbers of intratumoral effector T cells (T eff , cytotoxic and helper) significantly correlated with a better survival; regulatory T cells were infrequently present and not associated with GBM patient outcome. Interestingly, increased infiltration of T eff cells was related to the expression of ICAM-1 on the vessel surface. Transmigration of autologous T cells in vitro was markedly reduced in the presence of CAM-blocking antibodies. We found that TGF-b molecules impeded transmigration and downregulated CAM-expression on GBM-isolated endothelial cells; blocking TGF-b receptor signaling increased transmigration.Conclusions: This study provides comprehensive and novel insights into occurrence and regulation of T-cell infiltration in glioma. Specifically, targeting TGF-b1 and TGF-b2 might improve intratumoral T-cell infiltration and thus enhance effectiveness of immunotherapeutic approaches. Clin Cancer Res; 17(13); 4296-308. Ó2011 AACR.

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Spontaneous immune responses against glioma-associated antigens in a long term survivor with malignant glioma

Cited by 29 publications

References 31 publications

Cancer-testis and melanocyte-differentiation antigen expression in malignant glioma and meningioma

Cancer-testis and melanocyte-differentiation antigen expression in malignant glioma and meningioma

Perspectives on the immunologic microenvironment of astrocytomas

Effector T-Cell Infiltration Positively Impacts Survival of Glioblastoma Patients and Is Impaired by Tumor-Derived TGF-β

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