Local inhibition of natural killer cell activity promotes the progressive growth of intraocular tumors

Rajendra S. Apte, Elizabeth Mayhew, Jerry Y. Niederkorn

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

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 104 cells) and OCM-3 tumors (1 x 106, 5 x 106 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.

Original languageEnglish (US)
Pages (from-to)1277-1282
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume38
Issue number6
StatePublished - 1997

Fingerprint

Natural Killer Cells
Growth
Aqueous Humor
Neoplasms
Severe Combined Immunodeficiency
Subcutaneous Injections
Inbred C57BL Mouse
Nude Mice
Lymphoma
Cell Count
Antibodies

Keywords

  • anterior chamber
  • aqueous humor
  • natural killer
  • ocular melanoma

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Local inhibition of natural killer cell activity promotes the progressive growth of intraocular tumors. / Apte, Rajendra S.; Mayhew, Elizabeth; Niederkorn, Jerry Y.

In: Investigative Ophthalmology and Visual Science, Vol. 38, No. 6, 1997, p. 1277-1282.

Research output: Contribution to journalArticle

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AU - Mayhew, Elizabeth

AU - Niederkorn, Jerry Y.

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N2 - 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 104 cells) and OCM-3 tumors (1 x 106, 5 x 106 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.

AB - 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 104 cells) and OCM-3 tumors (1 x 106, 5 x 106 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.

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