A 'stealth effect': Adenocarcinoma cells engineered to express TRAIL elude tumor-specific and allogeneic T cell reactions

Mirella Giovarelli, Piero Musiani, Gianni Garotta, Reinhard Ebner, Emma Di Carlo, Yunsoo Kim, Paola Cappello, Laura Rigamonti, Paola Bernabei, Francesco Novelli, Andrea Modesti, Anna Coletti, Ann Kim Ferrie, Pier Luigi Lollini, Steve Ruben, Theodora Salcedo, Guido Forni

Research output: Contribution to journalArticlepeer-review

Abstract

BALB/c mammary adenocarcinoma cells engineered to express TNF-related apoptosis-inducing ligand (TRAIL)/APO-2 ligand (APO-2L) on their membrane (TSA-TRAIL) grow with kinetics similar to that of parental cells (TSA-pc) in vitro and in nu/nu mice. In contrast, TSA-TRAIL cells grow faster than TSA-pc in normal BALB/c mice. In DBA/2 mice, which differ from BALB/c mice at minor histocompatibility Ags, they also grow faster and display a higher percentage of tumor takes than TSA-pc. In fully histoincompatible C57BL/6 (B6) mice, TSA-TRAIL cells form evident tumors that are slowly rejected by most mice, but outgrow in a few. In contrast, TSA-pc cells are rejected at once by B6 mice. Since TRAIL/APO-2L induces apoptosis by interacting with a variety of specific receptors, this rapid growth in both syngeneic and allogeneic mice may be the result of an immunosuppressive mechanism. The following evidence supports this hypothesis: 1) TSA-TRAIL cells overcome the strong immunity against TSA-pc cells elicited in BALB/c mice by preimmunization with TSA cells engineered to release IL-4; 2) their rejection by B6 mice does not prime a CTL-mediated memory; 3) thymidine uptake by T lymphocytes unstimulated or stimulated by allogeneic cells is inhibited when TSA-TRAIL cells are added as third party cells; 4) CTL kill TSA-pc but not TSA-TRAIL cells in 48-h assays; and 5) activated lymphocytes interacting with TSA-TRAIL cells in vivo and in vitro undergo apoptosis.

Original languageEnglish
Pages (from-to)4886-4893
Number of pages8
JournalJournal of Immunology
Volume163
Issue number9
Publication statusPublished - 1999

ASJC Scopus subject areas

  • Immunology

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