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The interferon‐inducible transcription factor STAT1 is a tumor suppressor in various malignancies. We investigated sex‐specific STAT1 functions in colitis and colitis‐associated colorectal cancer (CRC) using mice with specific STAT1 deletion in intestinal epithelial cells (STAT1∆IEC). Male but not female STAT1∆IEC mice were more resistant to DSS‐induced colitis than sex‐matched STAT1flox/flox controls and displayed reduced intraepithelial infiltration of CD8+ TCRαβ+ granzyme B+ T cells. Moreover, DSS treatment failed to induce expression of T‐cell‐attracting chemokines in intestinal epithelial cells of male but not of female STAT1∆IEC mice. Application of the AOM‐DSS protocol for induction of colitis‐associated CRC resulted in increased intestinal tumor load in male but not in female STAT1∆IEC mice. A sex‐specific stratification of human CRC patients corroborated the data obtained in mice and revealed that reduced tumor cell‐intrinsic nuclear STAT1 protein expression is a poor prognostic factor in men but not in women. These data demonstrate that epithelial STAT1 is a male‐specific tumor suppressor in CRC of mice and humans.

Background CD97 is a member of the epidermal growth factor-seven transmembrane (EGF-TM7) receptor family and is dominantly expressed on immune cells and in a variety of malignant diseases. B7-H1 and B7-H3 are transmembrane proteins that are involved in suppression of the immune system. The aim of this study was to evaluate if these molecules are up-regulated in patients with cancer and change during chemotherapy. Materials and methods We analyzed cluster of differentiation (CD) protein expression levels on tumor cell lines and in blood samples of 37 patients with solid tumors at baseline and during chemotherapy; we correlated the serum levels of CD proteins with survival outcome. Results Levels of soluble CD97 proteins were significantly elevated in all three cancer types compared to healthy controls. Patients with colorectal cancer and those with high CD97 levels had a significantly worse prognosis. Conclusion This study showed a marked elevation of soluble CD97 expression in patients with certain cancer types and demonstrated definite changes in CD protein expression during chemotherapy in one patient with metastatic breast cancer.