Local inhibition of natural killer cell activity promotes the progressive growth of intraocular tumors
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R S Apte1, E Mayhew, J Y Niederkorn
1Graduate Program in Immunology, University of Texas Southwestern Medical Center, Dallas 75235-9057, USA.
Purpose:
To study the effect of aqueous humor (AH)-mediated inhibition of natural killer (NK) cell activity on intraocular tumor progression.
Methods:
Two NK-sensitive tumors, RMA-S lymphoma and OCM-3 uveal melanoma, were tested in vitro for susceptibility to NK cell-mediated lysis in the presence or absence of AH in conventional cytotoxicity assays. Various numbers of RMA-S and OCM-3 tumor cells were injected either subcutaneously or intracamerally into C57BL/6 severe combined immunodeficiency mice and BALB/c nude mice respectively and tumor growth was monitored. The role of NK cell-mediated cytotoxicity in controlling tumor growth was confirmed by depleting NK cells in severe combined immunodeficiency mice by administering anti-asialo GM1 antibodies before subcutaneous tumor injection.
Results:
AH significantly inhibited NK cell-mediated lysis of RMA-S and OCM-3 tumor cells in vitro and in vivo. NK sensitive RMA-S (1 x 10(4) cells) and OCM-3 tumors (1 x 10(6), 5 x 10(6) cells) were rejected after subcutaneous injection in C57BL/6 mice, whereas the same or even lower numbers of cells grew progressively in the eye. In vivo NK cell depletion resulted in progressive growth of subcutaneously injected RMA-S tumors at a dose rejected by mice with normal NK cell activity.
Conclusions:
AH inhibits NK cell activity in vitro and within the interior of the eye and prevents the rejection of NK-sensitive intraocular tumors.
Insights
Aqueous humor inhibits natural killer cell activity, preventing the rejection of intraocular tumors. This study reveals how the eye
Area of Science:
- Immunology
- Ophthalmology
- Oncology
Background:
- Natural killer (NK) cells are crucial for immune surveillance against tumors.
- The intraocular environment's effect on immune cell activity is not fully understood.
- Aqueous humor (AH) is the fluid within the anterior chamber of the eye.
Purpose of the Study:
- To investigate the impact of aqueous humor on natural killer cell activity.
- To determine how AH-mediated inhibition of NK cells affects intraocular tumor progression.
Main Methods:
- In vitro cytotoxicity assays assessed NK cell lysis of tumor cells (RMA-S lymphoma, OCM-3 uveal melanoma) with or without AH.
- Tumor cells were injected subcutaneously and intracamerally into immunodeficient mice.
- NK cell activity was depleted using anti-asialo GM1 antibodies to confirm its role in tumor rejection.
Main Results:
- Aqueous humor significantly inhibited NK cell-mediated lysis of both RMA-S and OCM-3 tumor cells in vitro and in vivo.
- Subcutaneously injected NK-sensitive tumors were rejected in immunocompetent mice, but grew progressively within the eye.
- Depletion of NK cells in vivo led to the progressive growth of tumors that are normally rejected.
Conclusions:
- Aqueous humor actively suppresses natural killer cell function within the eye.
- This suppression prevents the immune system from rejecting naturally occurring, NK-sensitive intraocular tumors.
- Findings highlight a mechanism by which the eye may evade immune responses against developing tumors.