Different Subsets of Tumor-Infiltrating Lymphocytes Correlate with Macrophage Influx and Monosomy 3 in Uveal Melanoma

Abstract

All studied subtypes of tumor-infiltrating immune cells were collectively increased and showed an association with monosomy of chromosome 3 suggesting that tumor intrinsic factors control the leukocyte influx, possibly through local chemokine secretion.

Inflammation in uveal melanoma

“…We recently observed that both CCL22 and CCL2 were expressed in freshly cultured uveal melanoma cells as well as in monocytes. 33 Furthermore, we observed that increased numbers of TAMs and lymphocytes, as well as HLA expression, were all associated with chromosome 3 loss (Figure 3). There is evidence that chromosome 3 is associated with an increased leukocyte population, but the molecules involved have not yet been identified.…”

“…The predominant cells are CD8 þ CTLs with a weaker presence of CD4 þ cells and also CD3 þ FoxP3 þ Tregs. 33 The number of infiltrating CD163 þ M2 macrophages is related to the number of Tregs, but it is not clear whether these cells interact. Different types of tumour-infiltrating leukocytes can affect each other's function.…”

Immunological aspect of the liver and metastatic uveal melanoma

“…These factors suppress T cell proliferation and effector function, and could induce immunosuppressive regulatory T (Treg) cells. + M2 macrophages [7,8] . Infiltration of immune cells occurs more frequently in epithelioid-celltype UM.…”

“…It has been reported that Treg cells are recruited into tumors by chemokines, CCL17 and CCL22 that are produced by M2 macrophages. Furthermore, tumor-produced CCL2 and CCL22 have a role not only in attracting tumor-promoting macrophages, but also in promoting their survival and M2 polarization [7] . While UM cells possess tumor-associated antigens and tumor-infiltrating CD4 + and CD8 + cells are present in the primary UM, Treg cells are also present in the tumor.…”

Antilymphangiogenic therapy to promote transplant survival and to reduce cancer metastasis: What can we learn from the eye?

“…Studies in mice revealed that depletion of macrophages during tumor induction prevented tumor growth, whereas in non-depleted mice all animals developed ocular tumors [116][117][118]. Next to TAMs in uveal melanoma CD8+ T-cells and CD3+FoxP3+ regulatory T-cells (Tregs) have been detected [119]. Tregs modulate other immune cells toward a tolerance state and high numbers of Tregs are associated with a poor prognosis [120].…”