AuthOr’s VIew AuthOr’s VIew

Both the prognostic evaluation and the therapeutic management of lung adeno-carcinoma patients currently rely on the tumor node metastasis staging system. Nevertheless, clinical outcomes after sur-gical resection are often unfavorable, even among patients presenting with early-stage disease. Accumulating evidence indicates that the tumor immune microenviron-ment constitutes a robust prognostic indi-cator. Thus, in some solid tumors, high levels of tumor-infiltrating CD4+ helper, CD8+ cytotoxic and CD45RO+ memory T lymphocytes have been associated with favorable clinical outcomes.1,2 Conversely, a high density of tumor-infiltrating FOXP3+ regulatory T cells (Tregs) often represents an unfavorable prognostic fac-tor.3 FOXP3+ Tregs are potent suppressors of adaptive antitumor immune responses and hence may sustain invasiveness and metastatic colonization. Recently, in two large independent cohorts of patients affected by Stage I lung adenocarcinoma (total n = 956), we found that a high relative proportion of FOXP3+ Tregs to CD3+ lymphocytes infiltrating the tumor stroma is an independent fac-tor of poor prognosis (Fig. 1A).4 Among the tumors infiltrated by a high density of FOXP3+ Tregs, high levels of CD3+ T cells were associated with better clinical out-comes than relatively scarce CD3+ T-cell Prognostic value of the immune microenvironment in lung adenocarcinom