Macrophages Are Vital in Spontaneous Intraocular Tumor Eradication

Boonman, Zita F. H. M.; Schurmans, Lucas R. H. M.; Rooijen, Nico van; Melief, Cornelis J.M.; Toes, René E. M.; Jager, Martine J.

doi:10.1167/iovs.05-1427

Cited by 29 publications

(34 citation statements)

References 27 publications

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“…29 However, not all TAMs support the growth of tumors, as there are multiple accounts of macrophages being tumoricidal and necessary for tumor rejection. [30][31][32] This again underscores the heterogeneity of macrophage populations and their influence on tumor growth or progression.…”

Section: Macrophages and Angiogenesismentioning

confidence: 80%

Effect of Senescence on Macrophage Polarization and Angiogenesis

Dace

Apte

2008

Rejuvenation Research

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There is mounting evidence that as the immune system ages, a progressive deterioration in normal function occurs. Termed immunosenescence, aging impacts both the innate and adaptive immune responses. This review discusses the age-related alterations in the innate immune system, with a specific focus on macrophages. The downstream effect of altered macrophage function on aberrant angiogenesis in the pathophysiology of age-related eye disease is also discussed. 177

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Section: Macrophages and Angiogenesismentioning

confidence: 80%

Effect of Senescence on Macrophage Polarization and Angiogenesis

Dace

Apte

2008

Rejuvenation Research

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“…A previously described technique for deposition of tumor cells into the anterior chamber (AC) of the mouse was applied with slight modifications (15,17). Mice were anesthetized with a mixture (ratio 1:1) of xylazine (Rompun 2%, Bayer, Leverkussen, Germany) and ketamine hydrochloride (Aescoket, Aesculaap, Boxtel, The Netherlands), given i.p.…”

Section: Intracameral Inoculation and Clinical Evaluationmentioning

confidence: 99%

“…We studied tumor growth postremoval of macrophages in an ocular tumor model (15)(16)(17). Because EspinosaHeidmann and Apte (7,8) showed that age influences macrophage polarization, we also determined whether tumor growth was different in young versus old mice and what the effect of macrophage depletion would be on tumor progression at different ages.…”

mentioning

confidence: 99%

In Aged Mice, Outgrowth of Intraocular Melanoma Depends on Proangiogenic M2-Type Macrophages

Ly¹,

Baghat²,

Versluis³

et al. 2010

The Journal of Immunology

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Macrophages are part of the tumor microenvironment and have been associated with poor prognosis in uveal melanoma. We determined the presence of macrophages and their differentiation status in a murine intraocular melanoma model. Inoculation of B16F10 cells into the anterior chamber of the eye resulted in rapid tumor outgrowth. Strikingly, in aged mice, tumor progression depended on the presence of macrophages, as local depletion of these cells prevented tumor outgrowth, indicating that macrophages in old mice had a strong tumor-promoting role. Immunohistochemistry and gene expression analysis revealed that macrophages carried M2-type characteristics, as shown by CD163 and peroxisome proliferator-activated receptor γ expression, and that multiple angiogenic genes were heavily overrepresented in tumors of old mice. The M2-type macrophages were also shown to have immunosuppressive features. We conclude that tumor-associated macrophages are directly involved in tumor outgrowth of intraocular melanoma and that macrophages in aged mice have a predisposition for an M2-type profile.

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“…CTL activity in both studies was not detected toward the respective target cells even though a mononuclear cell infiltrate was observed in rejecting tissue, and the processing and presentation of relevant peptides by host APCs were necessary to generate CD8 ϩ T effector cells (45). It bears noting that F4/80 ϩ macrophages are involved in rejecting Ad5E1 intraocular tumors (data not shown) and that the depletion of ocular macrophages with clodronate liposome injection results in progressive Ad5E1 tumor growth (11). This suggests that ocular APC function may be necessary for tumor Ag presentation to CD8 ϩ T cells and eventual tumor rejection in the eye.…”

Section: Discussionmentioning

confidence: 86%

“…However, ocular immune privilege can be circumvented. Ocular tumors can induce a robust systemic immune response that culminates in tumor rejection (7)(8)(9)(10)(11). Immune rejection of intraocular tumors follows two mutually divergent patterns.…”

mentioning

confidence: 99%

CD8+ T Cells Circumvent Immune Privilege in the Eye and Mediate Intraocular Tumor Rejection by a TNF-α-Dependent Mechanism

Dace

Chen

Niederkorn

2007

The Journal of Immunology

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Although intraocular tumors reside in an immune-privileged environment, T cells can circumvent immune privilege and mediate tumor rejection without inducing damage to normal ocular tissue. In this study, we used a well-characterized tumor, Ad5E1 (adenovirus type 5 early region 1), to analyze the role of CD8+ T cells in the pristine rejection of intraocular tumors. It has been previously documented that Ad5E1 tumor rejection can occur in the absence of CD8+ T cells. However, here we find that CD8+ T cells infiltrated intraocular Ad5E1 tumors in C57BL/6 mice. Surprisingly, CD8+ T cells from tumor-rejector mice could mediate intraocular tumor rejection following adoptive transfer to SCID mice. In determining the mechanisms behind CD8+ T cell-mediated tumor rejection, we discovered that antitumor CTL activity was neither observed nor necessary for rejection of the intraocular tumors. CD8+ T cells from rejector mice did not produce IFN-γ in response to Ad5E1 tumor Ags or use FasL to mediate intraocular tumor rejection. Also, CD8+ T cells did not use perforin or TRAIL, as CD8+ T cells from perforin knockout (KO) and TRAIL KO mice conferred protection to SCID recipient mice following adoptive transfer. We discovered that CD8+ T cells used TNF-α to mediate tumor rejection, because Ad5E1 tumor cells were highly sensitive to TNF-α-induced apoptosis and CD8+ T cells from TNF-α KO mice did not protect SCID mice from progressive Ad5E1 tumor growth. The results indicate that CD8+ T cells circumvent immune privilege and mediate intraocular tumor rejection by a TNF-α-dependent manner while leaving the eye intact and vision preserved.

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Macrophages Are Vital in Spontaneous Intraocular Tumor Eradication

Cited by 29 publications

References 27 publications

Effect of Senescence on Macrophage Polarization and Angiogenesis

Effect of Senescence on Macrophage Polarization and Angiogenesis

In Aged Mice, Outgrowth of Intraocular Melanoma Depends on Proangiogenic M2-Type Macrophages

CD8+ T Cells Circumvent Immune Privilege in the Eye and Mediate Intraocular Tumor Rejection by a TNF-α-Dependent Mechanism

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