“Tumor –induced senescence of T lymphocytes cells: a novel mechanism of immune evasion”.

MONTES CL; ORHUE V; CHAPOVAL A; STROME S; GASTMAN B

Miami.USA

Congreso; 94th Annual meeting of The American Association of immunologist.; 2007

American Association of immunologist

Tumor immune evasion[CM1]  exhibits passive and active components. Passive components include tumors becoming inconspicuous and resistant to immune-mediated killing. The active components consist of tumors induced cellular dysfunction, like apoptosis of immune effectors cells. We hypothesized that tumor infiltrating lymphocytes that encounter cancer at a low tumor:T cell ratio, for a short time, undergo senescence instead of apoptosis. Premature senescence is a form of cellular dysfunction that leads to the demise of the cell. We demonstrated that a high percentage of human T cells from healthy donors incubated with different tumor cell lines for 6 hours at a 1:1 Tumor /T cell ratio and then cultured for 7 days in media only, undergo senescence as judged by the incremental loss of CD27 and CD28 expression and telomere shortening. Cell to cell contact does not seem necessary in the induction of this process. We also showed increases in the senescence associated molecules (p53, p21 and p16) in TIST. In addition, TIST occurs equally in CD4+ and CD8+ cells and both cells types suppress the proliferation of CD3- stimulated or allogenic effector cells but do not express CD25 nor Foxp3. Increased levels of INF gamma, IL10 and IL6 suggest a role for these cytokines in TIST mediated immunosuppression. This novel mechanism of immune evasion has impact in both diagnostic and treatment aspects of cancer. Supported by Otorhinolaryngology Department.  [CM1]