Background/Objectives: The tumor microenvironment (TME) has emerged as a significant prognostic factor. This study aimed to identify prognostic factors by combining clinicopathologic parameters and the TME biomarkers in patients who underwent surgery following neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC). Methods: CD8⁺ T cells, CXCR3, CXCL10, and α-smooth muscle actin (α-SMA) were analyzed via immunohistochemical staining. We also incorporated AI-powered digital pathology to assess the spatial TME. The associations between these biomarkers, clinicopathologic parameters, and survival outcomes were evaluated. Results: CD8⁺ T cell expression, CXCR3 expression in tumor-infiltrating lymphocytes (TILs), and immune phenotypes were correlated. LARC patients with a high expression of CD8⁺ T cells, CXCR3 in TILs, and an inflamed phenotype had a significantly better prognosis than their counterparts did. In the multivariate analysis, the expression of CD8⁺ T cells and the inflamed/immune-excluded phenotype were significant tumor immune microenvironment (TiME) biomarkers for recurrence-free survival (RFS) but not for overall survival (OS). Notably, patients with the immune-desert phenotype had a poor prognosis regardless of pathologic stage, even if postoperative chemotherapy was administered (p < 0.001). Conclusions: CD8⁺ T cells and AI-powered immune phenotypes, alongside clinical factors, can guide personalized treatment in LARC patients receiving nCRT. A therapeutic strategy to modify the TiME after nCRT could help reduce recurrence after surgery.

The role of biomarkers in cancer treatment varies significantly depending on the cancer stage. Thus, in clinical practice, tailoring biomarkers to meet the specific needs and challenges of each cancer stage can increase the precision of treatment. Because they reflect underlying genetic alterations that influence cancer progression, copy number variation (CNV) biomarkers can play crucial prognostic roles. In our previous study, we identified potential survival-related genes for colorectal cancer (CRC) by analyzing CNV and gene expression data using a machine-learning approach. To further investigate the biological function of NRXN1, we assessed the use of RNA sequencing, phosphokinase assays, real-time quantitative PCR, and Western blot analysis. We found that NRXN1 copy number deletion was significantly associated with poor overall survival (OS) and recurrence-free survival (RFS), even in patients who received adjuvant chemotherapy. Compared with its expression in normal tissues, NRXN1 expression was lower in tumors, suggesting its potential role as a tumor suppressor. NRXN1 knockdown enhanced CRC cell viability and invasion, and transcriptome analysis indicated that the increased invasion was caused by GSK3β-mediated epithelial–mesenchymal transition. These findings highlight NRXN1 copy number deletion as a novel biomarker for predicting recurrence and survival in patients with resected colon cancer.

Background: We aimed to identify the risk factors for impaired cellular and humoral immunity after three doses of the SARS-CoV-2 vaccine. Methods: Six months after the third vaccine dose, T-cell immunity was evaluated using interferon-gamma release assays (IGRAs) in 60 healthy and 139 immunocompromised (IC) individuals, including patients with hematologic malignancy (HM), solid malignancy (SM), rheumatic disease (RD), and kidney transplantation (KT). Neutralizing antibody titers were measured using the plaque reduction neutralization test (PRNT) and surrogate virus neutralization test (sVNT). Results: T-cell immunity results showed that the percentages of IGRA-positive results using wild-type/alpha spike protein (SP) and beta/gamma SP were 85% (51/60) and 75% (45/60), respectively, in healthy individuals and 45.6% (62/136) and 40.4% (55/136), respectively, in IC individuals. IC with SM or KT showed a high percentage of IGRA-negative results. The underlying disease poses a risk for impaired cellular immune response to wild-type SP. The risk was low when all doses were administered as mRNA vaccines. The risk factors for an impaired cellular immune response to beta/gamma SP were underlying disease and monocyte%. In the sVNT using wild-type SP, 12 of 191 (6.3%) individuals tested negative. In the PRNT of 46 random samples, 6 (13%) individuals tested negative for the wild-type virus, and 19 (41.3%) tested negative with omicrons. KT poses a risk for an impaired humoral immune response. Conclusions: Underlying disease poses a risk for impaired cellular immune response after the third dose of the SARS-CoV-2 vaccine; KT poses a risk for impaired humoral immune response, emphasizing the requirement of precautions in patients.