The therapeutic implications of intratumoral regulatory T cells

G Dranoff - Clinical Cancer Research, 2005 - AACR
G Dranoff
Clinical Cancer Research, 2005AACR
In this issue of Clinical Cancer Research, Wolf and colleagues present compelling evidence
that underscores a key role for regulatory T cell–induced immune suppression in tumor
pathogenesis (1). Although most cancer patients mount innate and adaptive antitumor
reactions, the evolution of clinically evident disease implies a failure of host defense. The
analysis of endogenous antitumor responses may thus yield insights into the mechanisms
underlying cancer escape from immune control. As recent work in murine models …
In this issue of Clinical Cancer Research, Wolf and colleagues present compelling evidence that underscores a key role for regulatory T cell–induced immune suppression in tumor pathogenesis (1). Although most cancer patients mount innate and adaptive antitumor reactions, the evolution of clinically evident disease implies a failure of host defense. The analysis of endogenous antitumor responses may thus yield insights into the mechanisms underlying cancer escape from immune control. As recent work in murine models established that some host reactions mediate tumor protection (2), deciphering the pathways that restrain tumor immunity in cancer patients should further the development of immunotherapy. The crafting of genetic and biochemical techniques to characterize tumor antigens led to the realization that most cancer patients harbor in their peripheral blood T cells and antibodies that manifest specificity for autologous tumor. In some cases, primary and metastatic tumor deposits also elicit significant lymphocyte infiltrates. Together, these findings indicate that many cancers are sufficiently immunogenic to provoke nascent host responses. Longitudinal clinicopathologic investigations revealed that some endogenous reactions are of prognostic importance (3). Brisk intratumoral (but not peritumoral) T-cell infiltrates in early-stage melanomas are correlated with a reduced incidence of recurrent disease and decreased mortality after complete resection. Intratumoral T cells in follicular lymphomas and colon, renal cell, and ovarian carcinomas similarly are coupled to improved patient outcomes after surgery and chemotherapy. High titer antibodies to the tumor-associated antigen MUC-1 are also associated with increased survival in patients with early-stage breast cancer. Collectively, these results imply that whereas spontaneous host reactions might be inadequate to prevent tumor formation, some are linked to more profound and durable clinical benefits with conventional cancer therapy. An intriguing issue for further exploration is whether endogenous tumor immunity contributes in some way to the efficacy of standard treatments.
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