Predicting the Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Using Soluble Immune Checkpoints

Introduction: Personalizing neoadjuvant therapy for locally advanced rectal cancer (LARC) requires identifying biomarkers that predict treatment response. This study aims to evaluate soluble immune checkpoints (sICPs) as predictive markers for neoadjuvant treatment response in LARC patients located in the middle and lower rectum.Materials and Methods: This prospective study included patients diagnosed with clinical stage T3 or T4 rectal cancer (RC) based on pelvic magnetic resonance imaging, with or without pelvic lymph node involvement. The modified Ryan scoring system was used to assess the response to neoadjuvant chemoradiotherapy (nCRT). Blood samples were collected from all RC patients before initiating nCRT. Various sICPs (sCD25, 4-1BB, B7.2, free active TGF-beta 1, CTLA-4, PD-L1, PD-1, Tim-3, LAG-3, galectin-9), along with age, gender, stage, blood cell counts, and biochemical variables, were recorded and compared based on tumor regression grade (TRG).Results: Among 38 participants, lymphocyte count was higher, and platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and platelet count were lower in patients with complete/near-complete response (TRG 0/1). In addition, TRG 0/1 patients had significantly lower levels of soluble galectin-9 than TRG 2/3 patients. Furthermore, platelet count was the only parameter that showed a significant difference among the three groups (TRG 0/1, TRG 2, and TRG 3). PLR demonstrated the highest sensitivity and specificity, with >80% for both measures.Conclusions: Lymphocyte count, PLR, NLR, platelet count, and galectin-9 may help predict favorable neoadjuvant treatment response in LARC patients, although without providing a definitive outcome. Personalized therapy based on these markers could enhance treatment decision making in LARC management.