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Purpose: The purpose of this study was to assess the prognostic significance of the modified diagnostic biopsy-adapted immunoscore (mIS b ) in determining the outcomes for patients with locally advanced rectal cancer (LARC) in a neoadjuvant setting., Methods and Materials: We included 181 patients with LARC from a single subcenter of a prospective study comparing total neoadjuvant therapy (TNT) based on short-course radiation therapy with long-term chemoradiation therapy (CRT). Tumor biopsies at baseline were stained for CD8+ and CD3+ T-cell densities. The mIS b was developed using mean percentile of CD8+ T-cell density and CD8/CD3 ratio. Patients were classified into low (0%-25%), intermediate (>25%-70%), and high (>70%-100%) in both groups. The relativity among different lymphocytes and their correlation with survival were illustrated. Survival analyses and Cox regression models were used to compare the prognostic values of mIS b and diagnostic biopsy immunoscore for survival outcomes and to assess the role of mIS b in TNT and CRT subgroups, respectively., Results: In this study, 151 (83.4%) patients received surgery, and 30 (16.6%) followed a watch and wait strategy. A strong correlation was found between CD8+ and CD3+ T-cell densities (R = 0.86; P < .001), whereas a weak correlation was witnessed between CD8+ and CD8/CD3 ratio (R = 0.45). The 3-year disease-free survival for the entire cohort was 69.9%, with 57.2%, 68.6%, and 85.5% for the low, intermediate, and high mIS b groups, respectively (P = .01), whereas diagnostic biopsy immunoscore failed to distinguish survival outcomes. Multivariate analysis revealed mIS b to be an independent prognostic factor for disease-free survival in surgically treated patients (P = .01). Specifically, patients with high mIS b score showed longer progression-free survival than other subgroups in the TNT cohort (P = .049), but no significant difference was found in the CRT population., Conclusions: In this study, mIS b demonstrated significant prognostic value in patients with LARC receiving preoperative therapies, especially in the TNT subgroup. These findings may help tailor the intensity of neoadjuvant therapy for patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)