New Insights on the Relationship between Arginase-1, Tumor Associated Neutrophils, Perineural Invasion, Neoadjuvant therapy and Prognosis in Rectal Cancer Patients

Introduction: Rectal cancer is one of the most common cancers with a high epidemiologic burden. Need for new prognostic and predictive indicators and therapies is urgent in the field to improve clinical outcomes and gather a better understanding of the disease. Indicators such as Arginase-1 (produced also by neutrophils) that has been found to be a potent immuno-depressor (eg. T cell immunodepression), neural-tumor relation, eg. the schwann cells-tumor interaction (including the recalling of MDSC), that can act as immunosuppressors for instance through the increase in production of TGF beta. This paper aims to shed new light on this complex set of interactions and their possible roles in prognosis, predictivity and basis for new drugs discoveries. Methodology: As part of the project a quantitative analysis of tumor-associated neutrophils (TANs) on formalin embedded sections of rectal cancer using CD66b and ARG1 immunohistochemical staining was conducted. A total of 65 patients with histologically confirmed rectal adenocarcinoma were retrospectively included and stratified into four groups according to neoadjuvant treatment modality. Clinical and pathological data were collected from medical records, including: perineural invasion, neoadjuvant treatment received and progression-free survival (DFS). Conclusion and Discussion: Patients who did not undergo neoadjuvant therapy and had no perineural invasion from the tumor, had a statistically significant higher level of Arginase-1 and CD66b (neutrophils) and had a significantly worse prognosis (in terms of Disease-Free Survival) compared to patients who underwent neoadjuvanct therapy (especially compared to those who underwent exclusively radiotherapy). This last group of patients had a significantly higher amount of Arginase-1 and tumor associated neutrophils (TANs) compared to the first group. Including the patients whose tumors had perineural invasion, patients who didn’t undergo any neoadj therapy had a higher amount of Arginase 1 level in the tumor (with also a corresponding higher amount of CD66b cells).