Objective: This study aimed to determine the relationship between immunoscore, CD73 expression, and P53 binding protein 1 (53BP1) expression in patients with locally advanced rectal cancer who received neoadjuvant chemoradiotherapy (nCRT) at the time of diagnosis and after treatment. Material and Methods: The patients with locally advanced rectal cancer treated with nCRT at diagnosis and after treatment were included and immunoscore, CD73 expression, and 53BP1 expression were evaluated. Results: A total of 53 patients were included in the study. Higher immunoscore and CD73 expression in the stroma (p=0.029 and p=0.011, respectively) were observed in the pathology specimen, in patients who responded well to nCRT before neoadjuvant treatment than that in patients who did not respond well. However, no association was noted between CD73 expression in tumor cells and pathological response (p=0.874). The immunoscore at diagnosis (p=0.087), 53BP1 expression (p=0.871), and CD73 expression in the stroma (p=0.053) did not correlate with 3-year disease-free survival (DFS). In contrast, an association between CD73 expression level in tumor cells (p=0.014), tumor regression grade (p=0.041), and pathological complete response (p=0.011) and 3-year DFS was found to be statistically significant. Conclusion: Our study revealed that in addition to tumor-related factors, host-related factors were associated with treatment response. A significant association was observed between immunoscore, CD73 expression, and neoadjuvant therapy response. Markers that can predict the response to nCRT are still needed, and more studies should be conducted to figure out how well immunomarkers work in this field.