Eduardo Feliciangeli Moreno

This study examined the prognostic significance of immunoscore within consensus molecular subtypes (CMS), tumour budding (TB), and macrophage infiltration in colorectal cancer (CRC). A retrospective series was analysed using immunohistochemical staining, immunoscore evaluation, and CMS classification, according to established methods. Among the 255 patients with CRC, 34.9% had stage III disease. The CMS classification showed a predominance of CMS2/3 (69.4%), with relapse occurring across all the subtypes. Low immunoscore was frequent in conventional and serrated adenocarcinomas, as well as in CMS2/3, whereas MSI-H correlated with intermediate-high immunoscore. TB was prevalent in relapsed patients, particularly in CMS2/3 and CMS4, and was linked to serrated histology. TB of ≥ 20 foci was correlated with hepatic metastases. CD163+ macrophage infiltration was common in CMS1 and CMS2/3, and was associated with high immune scores. TB influenced overall and relapse-free survival, whereas CMS affected the overall survival. Immunoscore were not associated with survival. The associations identified between CMS subtypes and clinical as well as pathological characteristics enhance the understanding of CMS behaviour in clinical practice.

Background: Uveal melanoma is the most common primary intraocular cancer in adults; however, it remains rare. Despite its rarity, metastatic uveal melanoma poses significant treatment challenges. Tebentafusp, a T-cell receptor–bispecific molecule targeting glycoprotein 100 and CD3, has shown substantial survival benefits for HLA-A*02:01 positive patients. A notable complication associated with tebentafusp and similar immunotherapies is cytokine release syndrome (CRS), occurring in nearly 90% of tebentafusp-treated patients. Although typically mild, severe CRS (grade 3) affects around 1% of patients. The unpredictable nature of CRS complicates patient management during treatment. Methods: Monitoring cytokine levels, as key indicators of inflammation, may therefore be crucial for understanding and managing CRS. Advanced proteomic technologies enable the simultaneous measurement of multiple cytokines, providing a comprehensive view of inflammatory responses. Results: In this case, a patient with metastatic uveal melanoma developed CRS after tebentafusp treatment. A proteomic analysis tracked the cytokine changes from baseline to post-treatment, revealing significant elevations in inflammatory markers. Conclusions: These findings suggest potential strategies for more personalized CRS management in similar therapies.