**10. Conclusions**

Inflammation and immune responses play important roles in the progression of prostate cancer. Other inflammatory cells and immune cells could be also involved in the prostate cancer progression. T cells are also accumulated in prostate cancer of a diet-induced obese Hi-Myc mice [77]. The cytotoxic

function of NK cells to prostate cancer cells is inhibited by humoral factors from adipocytes [78]. These local inflammatory cells are orchestrated by several signalings from immune cells, adipocytes, or prostate cancers. Prostate cancer cells stimulated by adipokines or saturated fatty acid could change the local immune profile in the backgrounds of obesity [79]. The interplay between prostate cancer and immune cells is a "chicken and egg" situation. Another possible mechanism to affect prostate cancer in obesity could be an intestinal microbiome. High-fat diet changes the intestinal microbiome and enhances colorectal cancer and liver cancer [80,81]. The microbiome could modulate the host immune system, and these changes in the immune system might have an effect on distant prostate cancer. Murine immune systems are different from human, and all the findings in mice model could not be extrapolated to human prostate cancer. However, common mechanisms would exist also in human prostate cancer. Further analysis in mice model would give new insights into the mechanisms of the progression of prostate cancer enhanced by obesity and inflammation. Interventions to address systemic and/or local inflammation and a change in lifestyle may be therapeutic for prostate cancer.

**Author Contributions:** Conceptualization, K.F. and N.N.; methodology, K.F.; formal analysis, T.H.; investigation, M.M.; resources, K.F.; data curation, T.H.; writing—original draft preparation, K.F.; writing—review and editing, T.H. and M.M.; visualization, K.F. and T.H.; supervision, N.N.; project administration, K.F.; funding acquisition, K.F., T.H., M.U. and N.N.

**Funding:** This research was funded by JSPS KAKENHI, gran<sup>t</sup> number JP16K20137, JP18K16693.

**Conflicts of Interest:** The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
