The tumor microenvironment contains a complex network of cytokines that contribute to the nature of intratumoral immune reactions. In a study reported in Science Translational Medicine, Mlecnik and colleagues assessed chromosomal gains and losses and expression of 59 cytokines and receptors and their functional networks in colorectal cancer.
The investigators identified changes in local expression of 13 cytokines. Patients with metastatic disease exhibited increased frequency of deletions of cytokines from chromosome 4.
In particular, interleukin (IL)-15 deletion was associated with reduced IL-15 expression, higher risk of tumor recurrence, and reduced patient survival. Decreased IL-15 expression was associated with reduced local proliferation of B and T lymphocytes, and patients with proliferating B and T cells at the invasive margin and within the tumor center had significantly prolonged disease-free survival.
The investigators concluded, “These results delineate chromosomal instability as a mechanism of modulating local cytokine expression in human tumors and underline the major role of IL-15. Our data provide further mechanisms resulting in changes of specific immune cell densities within the tumor, and the importance of local active lymphocyte proliferation for patient survival.” ■
Mlecnik B, et al: Sci Transl Med 6:228ra37, 2014.