Cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) are important components of the tumor microenvironment, which have been reported to localize in colorectal carcinomas where they promote tumor progression. One of the crucial effects they exerted is immune-suppression, which was reported recently, however, the overall mechanism has not been fully addressed. In this study, it was shown that TAMs were enriched in colorectal cancer, and their infiltration was associated with VCAM-1 expression. Human colorectal cancer-derived CAFs can promote the adhesion of monocytes by up-regulating VCAM-1 expression in colorectal cancer cells. Furthermore, CAFs can attract monocytes by secreting IL-8 rather than SDF-1 and subsequently promote M2 polarization of macrophages, which synergize with CAFs in suppressing the functioning of natural killer (NK) cells. It was also found that CAFs promoted M2 macrophages recruitment in tumor tissue in vivo, and after VCAM-1 knocking-down in tumor cells or depletion of macrophages, the pro-tumor effect of CAFs was partly abolished, but no change was observed in NK cells infiltration. Collectively, the findings in this work show that TAMs and CAFs function synergistically in the tumor microenvironment and have the capacity to regulate NK cells in colorectal cancer and this presents a novel mechanism.

PurposeIn the present study, we investigated the incidence of cardiotoxicity within 5 years of trastuzumab treatment and evaluated potential risk factors in clinical practice.MethodsThe study cohort included 415 patients diagnosed with early breast cancer (EBC). Cardiotoxicity incidence was evaluated in patients receiving trastuzumab and those who did not. Multivariate Cox proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals of potential risk factors for trastuzumab-related cardiotoxicity after appropriate adjustments.ResultsIncidence of cardiotoxicity in patients treated with trastuzumab was significantly higher than that in controls (23.7% vs. 10.8%, p<0.001). This result was adjusted for factors that might increase the risk of cardiotoxicity, such as history of coronary artery diseases or the use of anthracyclines for more than four cycles.ConclusionOur findings indicated that treatment with trastuzumab was strongly associated with cardiotoxicity in EBC patients.

Ovarian cancer is a kind of gynecological malignancy with high mortality. Ferroptosis is a new type of iron-dependent cell death characterized by the formation of lipid peroxides and excessive accumulation of reactive oxygen species. Studies have shown that ferroptosis modulates tumor genesis, progression, and invasion, including ovarian cancer. Based on the mRNA expression data from TCGA, we construct a scoring system using consensus clustering analysis, univariate Cox regression analysis, and least absolute selection operator. Then, we systematically evaluate the relationship between score and clinical characteristics of ovarian cancer. The result from the prediction of biofunction pathways shows that score serves as an independent prognostic marker for ovarian cancer and affects tumor progression by modulating tumor metastasis. Moreover, immunocytes such as activated CD4 T cell, activated CD8 T cell, regulatory T cells, macrophage, and stromal cells, including adipocytes, epithelial cells, and fibroblast infiltrate more in the tumor microenvironment in a high-score group, indicating ferroptosis can also affect tumor immune landscape. Critically, four potentially sensitive drugs, including staurosporine, epothilone B, DMOG, and HG6-64-1 based on the scores, are predicted, and DMOG is recognized as a novel targeted drug for ovarian cancer. In general, we construct the scoring system based on ferroptosis-related genes that can predict the prognosis of ovarian cancer patients and propose that ferroptosis may affect ovarian cancer progression by mediating tumor metastasis and immune landscape. Novel drugs to target ovarian cancer are also predicted.