Targeting Tumor-Associated Macrophages in Cancer.

Macrophages are phagocytes that serve as a first line of defense against pathogenic insults to tissues. These innate immune cells mount proinflammatory responses to pathogens and repair damaged tissues. However, tumor-associated macrophages (TAMs) express cytokines and chemokines that can suppress antitumor immunity and promote tumor progression.

Integrin CD11b activation drives anti-tumor innate immunity.

Myeloid cells are recruited to damaged tissues where they can resolve infections and tumor growth or stimulate wound healing and tumor progression. Recruitment of these cells is regulated by integrins, a family of adhesion receptors that includes integrin CD11b. Here we report that, unexpectedly, integrin CD11b does not regulate myeloid cell recruitment to tumors but instead controls myeloid cell polarization and tumor growth.

STAT1 is a sex-specific tumor suppressor in colitis-associated colorectal cancer.

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 ). Male but not female STAT1 mice were more resistant to DSS-induced colitis than sex-matched STAT1 controls and displayed reduced intraepithelial infiltration of CD8 TCRαβ granzyme B T cells.

EGFR in Tumor-Associated Myeloid Cells Promotes Development of Colorectal Cancer in Mice and Associates With Outcomes of Patients.

Background & Aims: Inhibitors of the epidermal growth factor receptor (EGFR) are the first-line therapy for patients with metastatic colorectal tumors without RAS mutations. However, EGFR inhibitors are ineffective in these patients, and tumor level of EGFR does not associate with response to therapy. We screened human colorectal tumors for EGFR-positive myeloid cells and investigated their association with patient outcome.

Myeloid promotes formation of colitis-associated colorectal cancer in mice.

Myeloid cells lacking promote antitumor responses of NK and T cells but it is unknown if this crosstalk affects development of autochthonous tumors. We deleted in murine myeloid cells (STAT3) and examined the effect on the development of autochthonous colorectal cancers (CRCs). Formation of Azoxymethane/Dextransulfate (AOM/DSS)-induced CRCs was strongly suppressed in STAT3 mice.

Induction of colorectal cancer in mice and histomorphometric evaluation of tumors.

Colorectal cancer (CRC) originates from the epithelial cells lining the colon or rectum of the gastrointestinal tract and represents the third most common form of cancer worldwide. CRC is frequently associated with Colitis Ulcerosa or Crohn's Disease demonstrating the tumor-promoting role of inflammation. Colorectal tumor cells establish heterotypic interactions with inflammatory cells and cancer-associated fibroblasts in the tumor stroma that support tumor angiogenesis and are essential for tumor progression.