Perspectives on the immunologic microenvironment of astrocytomas

Hewedi, Iman H.; Radwan, Nehal A.; Shash, Lobna S; Elserry, Tarek

doi:10.2147/cmar.s48942

Cited by 16 publications

(16 citation statements)

References 17 publications

(22 reference statements)

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“…[11] The results of the current study were in agreement with Strojnik et al, 2010 Results that stated that, the majority (about 85%) of the studied cases expressed CD68 to various extents. (+) staining was found in 64% in low grade astrocytoma (grade I and grade II).They stated that staining for CD68 in high grade astrocytoma (grade III&IV) was significantly more pronounced than in the low grade astrocytoma (grade I&II).…”

Section: Discussionsupporting

confidence: 93%

Immunohistochemical Expression of Cluster of Differentiation-68(cd-68) and Ki-67 in Astrocytomas

Elkateb

Mostafa

Salah

et al. 2014

Zagazig University Medical Journal

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Background: Astrocytoma is common primary malignant brain tumors which arise from immortalized astrocytes. In astrocytoma microglia density is higher than in normal brain, and microglia increase in number according to the grade of malignancyIntense CD68 staining was marginally significant prognosticator for shorter survival.Since proliferative activity is a reliable method to assess tumour biology. Ki-67/MIB-1 has proven to be of prognostic and diagnostic power in astrocytic tumours and shown to correlate with tumour grade. Aim: This study was conducted to detect immunohistochemical expression of CD-68 and Ki-67 in astrocytoma and assessing their relation to proliferative activity and prognosis of such tumors. Methods: Thirty representative cases; 30 cases of astrocytoma examined immunohistochemically using antibodies against CD-68 and Ki-67. Results: CD-68 was positive in 73.3% of astrocytoma cases and it was negative in 26.7%. LowKi-67LI was found in low grade astrocytoma and high Ki-67 LI was found in high grade astrocytoma. Conclusion: CD-68 and Ki-67 were the most useful IHC markers in the discrimination of different grades of astrocytoma and predict proliferative activity and prognosis of such tumors.

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Section: Discussionsupporting

confidence: 93%

Immunohistochemical Expression of Cluster of Differentiation-68(cd-68) and Ki-67 in Astrocytomas

Elkateb

Mostafa

Salah

et al. 2014

Zagazig University Medical Journal

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“…17,18,28,38 With the presence of this cell origin-dependent TATE and its dissociation from other peripheral blood elements, the infiltration of eosinophils in astrocytomas seems to be actively involved in their pathogenesis other than a passive reactive process. 12,25 The major finding of our study is that eosinophils are commonly present in pediatric PAs but rarely (only one 20-year-old patient) in adult PAs. This age-dependent finding is consistent with that of our other study showing eosinophils in AT/RTs of all four patients younger than 2 years.…”

Section: Discussionmentioning

confidence: 68%

“…The frequency and degree of perivascular lymphoid infiltrates in PAs seen here are similar to those of previously published series. 24,25 While glomeruloid vasculature was often noted in PAs, 16 a few PAs contained microfoci of extravasated erythrocytes or microhaemorrhages with occasional hemosiderin deposition. 26…”

Section: Pilocytic Astrocytomasmentioning

confidence: 99%

Eosinophil Infiltrates in Pilocytic Astrocytomas of Children and Young Adults

Rashidipour

Wilson

et al. 2014

Can. J. Neurol. Sci.

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Objective: Eosinophils may affect each stage of tumour development. Many studies have suggested that tumour-associated tissue eosinophilia (TATE) is associated with favourable prognosis in some malignant tumours. However, only a few studies exist on TATE in central nervous system (CNS) tumours. Our recent study exhibited eosinophils in atypical teratoid/rhabdoid tumours (AT/RTs), pediatric malignant CNS tumours with divergent differentiation. This study examines eosinophils in pilocytic astrocytomas (PAs). Methods: The study included 44 consecutive cases of patients with PAs and no concurrent CNS inflammatory disease. Results: We found eosinophils in 19 (43%) of 44 PAs (patient age range, 0.5-72 years). Eosinophils were intratumoural and clearly distinguishable. The density of eosinophils was rare to focally scattered. PAs containing eosinophils were located throughout the CNS. Furthermore, eosinophilic infiltration was identified in 18 (62%) of 29 pediatric (age range, 0.5-18 years) PAs but only 1 (7%) of 15 (p < 0.001, significantly less) adult (age range, 20-72 years) PAs. Eosinophilic infiltration showed no significant differences between PAs with and without MRI cystic formation, surgical procedures, or PAs with and without leptomeningeal infiltration. In comparison, eosinophils were absent in 10 pediatric (age range, 0.5-15 years) ependymomas (or anaplastic ependymomas). Conclusions: These results suggest that eosinophils are common in pediatric PAs but rare in adult PAs. This difference is probably related to the developing immune system and different tumour-specific antigens in children. TATE may play a functional role in the development of pediatric PAs, as well as some other pediatric CNS tumours such as AT/RTs. RÉSUMÉ: Infiltrats éosinophiles dans les astrocytomes pilocytiques de l'enfant et du jeune adulte. Objectif: Les éosinophiles peuvent influencer chaque stade de l'évolution tumorale. Selon plusieurs études, l'éosinophilie tissulaire associée à certaines tumeurs malignes (ÉTAT) comporterait un pronostic favorable. Cependant, peu d'études sur l'ÉTAT de tumeurs du système nerveux central (SNC) ont été réalisées. Nous avons démontré récemment la présence d'éosinophiles dans des tumeurs tératoïdes/rhabdoïdes atypiques (TT/RA), des tumeurs malignes du SNC chez l'enfant avec différentiation divergente. Cette étude examine la présence d'éosinophiles dans les astrocytomes pilocytiques (APs). Méthode: Nous avons étudié 44 patients consécutifs atteints d'un AP, sans maladie inflammatoire concomitante du SNC. Résultats: Nous avons retrouvé des éosinophiles dans 19 (43%) des 44 AP. L'âge des patients atteints de ces tumeurs allait de 0,5 à 72 ans. Les éosinophiles étaient intratumoraux et clairement identifiables. Leur densité était variable, parfois rares ou en foyers dispersés. Les AP contenant des éosinophiles étaient localisés dans tout le SNC. De plus, une infiltration par des éosinophiles a été observée dans 18 (62%) des 29 AP chez les patients d'âge pédiatrique (écart de 0,5 à 18 ans), mais...

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“…In his seminal 1952 paper describing glioblastoma histology, Klatzo observed, “In the majority of tumors studied there was extensive microglial reaction […] resting forms were infrequently seen”. 10 We have more recently come to understand that these immune cell populations are composed of bone marrow-origin monocytes, 21 , 22 monocyte-derived macrophages, and microglia, 19 , 23 – 29 and neutrophils. 21 , 30 – 35 Estimates vary that these bone marrow-derived cells or nonmalignant microglia comprise 10%–30% of the total glioblastoma tumor mass, 12 , 23 , 26 , 36 , 37 but there is general agreement that MLCs make up a considerable percent of total mass 38 and MLCs have an established role in glioblastoma growth.…”

Section: Glioblastoma Are Heavily Infiltrated By Blood Monocytesmentioning

confidence: 99%

“… 18 Hewedi et al recognize “glioblastoma therapies should address this key CD68-positive [ie, monocyte/macrophage] population”. 19 We propose targeting MCP-1, a 13 kDa signaling peptide, synonymous with CC-chemokine ligand 2, which binds to outer cell membrane receptors CCR2 and/or CCR4 on MLCs and facilitates glioblastoma–microglia interaction.…”

Section: Introductionmentioning

confidence: 99%

Toward a noncytotoxic glioblastoma therapy: blocking MCP-1 with the MTZ Regimen

Salacz¹,

Kast²,

Saki³

et al. 2016

OTT

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To improve the prognosis of glioblastoma, we developed an adjuvant treatment directed to a neglected aspect of glioblastoma growth, the contribution of nonmalignant monocyte lineage cells (MLCs) (monocyte, macrophage, microglia, dendritic cells) that infiltrated a main tumor mass. These nonmalignant cells contribute to glioblastoma growth and tumor homeostasis. MLCs comprise of approximately 10%–30% of glioblastoma by volume. After integration into the tumor mass, these become polarized toward an M2 immunosuppressive, pro-angiogenic phenotype that promotes continued tumor growth. Glioblastoma cells initiate and promote this process by synthesizing 13 kDa MCP-1 that attracts circulating monocytes to the tumor. Infiltrating monocytes, after polarizing toward an M2 phenotype, synthesize more MCP-1, forming an amplification loop. Three noncytotoxic drugs, an antibiotic – minocycline, an antihypertensive drug – telmisartan, and a bisphosphonate – zoledronic acid, have ancillary attributes of MCP-1 synthesis inhibition and could be re-purposed, singly or in combination, to inhibit or reverse MLC-mediated immunosuppression, angiogenesis, and other growth-enhancing aspects. Minocycline, telmisartan, and zoledronic acid – the MTZ Regimen – have low-toxicity profiles and could be added to standard radiotherapy and temozolomide. Re-purposing older drugs has advantages of established safety and low drug cost. Four core observations support this approach: 1) malignant glioblastoma cells require a reciprocal trophic relationship with nonmalignant macrophages or microglia to thrive; 2) glioblastoma cells secrete MCP-1 to start the cycle, attracting MLCs, which subsequently also secrete MCP-1 perpetuating the recruitment cycle; 3) increasing cytokine levels in the tumor environment generate further immunosuppression and tumor growth; and 4) MTZ regimen may impede MCP-1-driven processes, thereby interfering with glioblastoma growth.

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Perspectives on the immunologic microenvironment of astrocytomas

Cited by 16 publications

References 17 publications

Immunohistochemical Expression of Cluster of Differentiation-68(cd-68) and Ki-67 in Astrocytomas

Immunohistochemical Expression of Cluster of Differentiation-68(cd-68) and Ki-67 in Astrocytomas

Eosinophil Infiltrates in Pilocytic Astrocytomas of Children and Young Adults

Toward a noncytotoxic glioblastoma therapy: blocking MCP-1 with the MTZ Regimen

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