The invasive margin of early-stage human colon tumors is infiltrated with neutrophils of an antitumoral phenotype.

Neutrophils infiltrate several types of cancer; however, whether their presence is associated with disease progression remains controversial. Here, we show that colon tumors overexpress neutrophil chemoattractants compared to healthy tissues, leading to their recruitment to the invasive margin (IM) and the central part (CT) of colon tumors. Of note, tumor-associated neutrophils (TAN) expressing TNFα, which usually represents an antitumoral phenotype, were predominantly located in the IM. TAN from the IM displayed an antitumoral phenotype with higher ICAM-1 and CD95 expression than neutrophils from healthy adjacent tissues (HAT). A higher Neutrophil-Lymphocyte Ratio (NLR) was found at later stages compared to the early phases of colon cancer. A NLR ≤ 3.5 predicted tumor samples had significantly more neutrophils at the IM and the CT. Moreover, TAN at the IM of early-stage tumors showed higher ICAM-1 and CD95 expression. Co-culture of colon cancer cell lines with primary neutrophils induced ICAM-1 and CD95 expression, confirming our in situ findings. Thus, our data demonstrate that TAN with an antitumoral phenotype characterized by high ICAM-1 and CD95 expression infiltrate the IM of early-stage colon tumors, suggesting that these cells can combat the disease at its early courses. The presence of TAN with antitumoral phenotype could help predict colon cancer patients' outcomes.