Figure 3.

Schematic summary of key transitions documented relating to cytokines and immune cells during testicular germ cell tumor progression indicate their involvement in the progressive changes that underpin testicular neoplasia. (A) In normal spermatogenesis, the number of resident immune cells present in the testicular interstitium is low relative to other somatic cell types. (B) Tubules containing even a few GCNIS cells are associated with changes in the cytokine environment; GCNIS cells themselves may be the source of significant interleukin-6 (IL6) and other cytokines that influence immune cell behaviors. (C) As the number of GCNIS cells increase, different types of immune cells infiltrate the testis, and the local cytokine profile transitions to a “neoplastic pattern.” Direct contact with immune cells may enhance cytokine production by GCNIS cells, yielding an environment which facilitates blood–testis barrier disruption and tumor progression. (D) In seminoma, many different types of immune cells and immune cell clusters [mainly comprised of B cells and CD11c+ dendritic cells (DCs)] are present, and characteristic “neoplastic” cytokine microenvironment is detectable that likely facilitates tumor progression. IL6 and other cytokines may be crucial as maintenance and progression factors. Adapted from Ref. (107).