Collectively, these data demonstrate that the IL-17-CXCR2 axis facilitates the recruitment of neutrophils to the tumor sites, thus allowing them to play a cancer-promoting role in cancer progression.
Here, we delve into the dichotomous roles of IL-17 in cancer and provide insight into the tumor microenvironment conducive for successful IL-17-based γδ and Th17 cell immunotherapy.
Moreover, the levels of serum interleukin-6 (IL-6) and IL-17 in patients with gastric cancer were higher than those in normal controls, and the higher the tumor stage, the higher the expression levels.
Our data not only provide useful insights into the clinical intervention of the growth and metastasis of the tumors (such as OvCa) that are prone to growth and metastasis in an adipocyte-rich microenvironment (ARM) but also provides new insights into the roles of IL-17A in tumor progression and immunomodulatory therapy of OvCa.
IL-17 expression was significantly increased in the tumor tissues and margins compared with that in the normal tissues, which was confirmed by immunohistochemical staining.
Although there was no role of IL‑17A in promoting in vitro cell proliferation, IL‑17A markedly increased the tumor growth of Huh7.5 cells in both subcutaneous and orthotopic xenograft models with increased vascularization.
Passive smoking significantly reduced the levels of FoxP3 (Forkhead/winged helix transcription factor) and tumor growth factor-β, which were associated with Treg cells, and increased the levels of interleukin-17A and interleukin-23, which were associated with Th17 cells.
Administration of antibiotics or a neutralizing antibody against IL17 to neutrophil-deficient mice resulted in development of less-invasive tumors compared with mice given vehicle.
Remarkably, knockdown of IL-17RA led to a significantly decreased capability of B16F10 cells to form tumors in vivo, similar to that in IL-17-deficient mice.
Furthermore, an increase in intratumoral pDCs was associated with increased intratumoral infiltration of Foxp3<sup>+</sup> regulatory T cells and IL-17-producing cells and correlated with tumor vascular density.
Tumor-educated MAIT cells significantly upregulated inhibitory molecules like PD-1, CTLA-4, TIM-3, secreted significantly less IFNγ and IL17, and produced minimal granzyme B and perforin while shifting to produce tumor-promoting cytokines like IL8.
We previously reported that T<sub>H</sub>17 cells and IL-17 mediate resistance to anti-VEGF therapy by inducing recruitment of immunosuppressive and proangiogenic myeloid cells to the tumor microenvironment.
Further understanding of the relationship between the IL-17/IL-17R axis and the tumour inflammatory microenvironment may reveal new therapeutic targets.
These interactions between MDSCs and T cells support tumor growth because IL-17 is tumorigenic in many cancer types and regulatory T cells suppress antitumor T cells.
Interestingly, donor-derived IL-17A acted directly on myeloma cells expressing the IL-17 receptor to induce a transcriptional landscape that promoted tumor growth and immune escape.
Increasing evidence has demonstrated that IL-17-producing γδ T cells (γδ T17) play a tumor-promoting role in a series of cancers via various mechanisms in mice and human cancers, though the relationship between γδ T17 and human tumors has yet to be extensively characterized and established.
The results showed that IL-17 could not only enhance the proliferation and migration of cultured glioma cells (in vitro), but also promote the tumor formation of glioma cells in BALB/c nude mice (in vivo).