Tumor Immunity in Perforin-Deficient Mice: A Role for CD95 (Fas/APO-1)
| Autor: | Ruben Orda, Jie Hui Li, Gideon Berke, Dalia Rosen, Ilya Markon, Sergey Keidar |
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| Rok vydání: | 2000 |
| Předmět: |
Cytotoxicity
Immunologic Pore Forming Cytotoxic Proteins Immunology chemical and pharmacologic phenomena Carcinoma Lewis Lung Mice In vivo Immunity hemic and lymphatic diseases Tumor Cells Cultured Animals Immunology and Allergy fas Receptor Mice Knockout Mice Inbred BALB C Membrane Glycoproteins biology Perforin Lewis lung carcinoma hemic and immune systems Fas receptor Up-Regulation Killer Cells Natural Mice Inbred C57BL CTL Granzyme Mice Inbred DBA Tumor progression biology.protein Cancer research biological phenomena cell phenomena and immunity Cell Division Neoplasm Transplantation T-Lymphocytes Cytotoxic |
| Zdroj: | The Journal of Immunology. 164:3229-3235 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | CTL and NK cells use two distinct cytocidal pathways: 1) perforin and granzyme based and 2) CD95L/CD95 mediated. The former requires perforin expression by the effectors (CTL or NK), whereas the latter requires CD95 (Fas/APO-1) expression by the target. We have investigated how these two factors contribute to tumor immune surveillance by studying the immunity of perforin-deficient mice against the progressor C57BL/6 Lewis lung carcinoma 3LL, which expresses no CD95 when cultured in vitro. Unexpectedly, the results indicated that the perforin-independent CD95L/CD95 pathway of CTL/NK plays a role in acting against D122 and Kb39.5 (39.5) high and low metastatic sublines, respectively, derived from the 3LL tumor. Although no membrane-bound CD95 was detected on cultured D122 and 39.5 cells, surface CD95 expression on both D122 and 39.5 was considerably up-regulated when the tumors were grown in vivo. A similarly enhanced expression of CD95 was observed with three additional tumors; LF−, BW, and P815, injected into syngeneic and allogeneic mice. The finding of up-regulated CD95 expression on tumor cells placed in vivo suggests that a CD95-based mechanism plays a role in tumor immunity at early stages of tumor growth. Consequently, the progressive down-regulation of CD95 expression during tumor progression may indeed be an escape mechanism as previously reported. Together, these results suggest a role for CD95-dependent, perforin-independent immunity against certain tumors. |
| Databáze: | OpenAIRE |
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