Tumor-associated macrophages confer resistance to chemotherapy (Trifluridine/Tipiracil) in digestive cancers by overexpressing thymidine phosphorylase.

Pyrimidine analogs are part of the first-line chemotherapy regimen for gastrointestinal cancers. Trifluridine combined with tipiracil, a specific thymidine phosphorylase inhibitor, in TAS-102 has recently emerged as a potential alternative in the face of primary or secondary chemoresistance to 5-fluorouracil. Despite its promise, we report that macrophage-specific overexpression of thymidine phosphorylase results in macrophage-induced chemoresistance to TAS-102 that is insensitive to tipiracil inhibition.

Metabolic reprogramming of hypoxic tumor-associated macrophages through CSF-1R targeting favors treatment efficiency in colorectal cancers.

Background: Tumor-associated macrophages participate in the complex network of support that favors tumor growth. Among the various strategies that have been developed to target these cells, the blockade of the colony-stimulating factor 1 receptor (CSF-1R) receptor is one of the most promising ones. Here, we characterize the resulting state of human macrophages exposed to a CSF-1R kinase inhibitor.

Impact of obesity on morbidity and oncologic outcomes after total mesorectal excision for mid and low rectal cancer.

Background: A recent meta-analysis showed that obesity increased the conversion rate and postoperative morbidity of rectal cancer surgery, but did not influence pathological results. However, this meta-analysis included patients with cancer of the upper rectum and had many biases. The aim of the present retrospective study was to investigate the impact of obesity, defined as a body mass index (BMI) ≥ 30 kg/m, on postoperative morbidity and short- and long-term oncologic outcomes of total mesorectal excision for mid and low rectal cancer in consecutive patients.