The interplay between
tumors and their immunologic microenvironment is complex and difficult to decipher, but its understanding is of seminal importance for the development of novel prognostic markers and therapeutic strategies. This chapter discusses
tumor-immune interactions in several human
cancers that illustrate various aspects of this complexity and proposes an integrated scheme of the impact of local immune reactions on clinical outcome. Thus, the fact that a strong infiltration of memory T cells with a Th1 and cytotoxic pattern is the strongest predictor for recurrence and
metastasis is exemplified in
colorectal cancer in which intratumoral
chemokines shape an efficient immune reaction. Based on these data, we propose an immune score that predicts recurrence in early stage (UICC-TNM stage I-II)
cancers. Studies on non-small
lung cancers have confirmed findings of
colorectal cancers and have addressed the question of the sites where antitumor immune reactions may take place.
Tertiary lymphoid structures (TLS) adjacent to the
tumor nest are sites of intense activity with mature dendritic cells in contact with T cells and germinal-like centers with proliferating B cells. The large number of these TLS being correlated with disease specific and overall survival tempts to postulate that they are privileged sites to mount an efficient antitumor reaction.
Inflammation is a major component of human
tumors and chronic
inflammation is generally of bad prognosis. Head and
neck cancers are highly inflammatory and two ways to modulate
inflammation in these diseases are presented here: soluble
IL-15 receptor α (IL-15 Rα) increases the pro-inflammatory effect of
IL-15 and aggravates
inflammation resulting in poor prognosis when found at high levels in the plasma of patients. By contrast, infiltration of regulatory T cells is paradoxically beneficial for local control of head and neck
tumors, probably by "cooling down" the inflammatory process. The modulation of other aspects of innate immunity may also result in paradoxical effects such as the signaling through
Toll like receptors 7 and 8 expressed on lung
tumor cells which induce an aggressive tumoral phenotype. Finally, the analysis of primary
intraocular lymphoma, which develops in the eye, exemplifies the induction of an antitumor immune reaction in an "immune sanctuary," presenting all the complexities of the
tumor-immune interplay in "open" tissues such as the colon or the lung.