TCF1-positive and TCF1-negative TRM CD8 T cell subsets and cDC1s orchestrate melanoma protection and immunotherapy response.

BACKGROUND: Melanoma, the most lethal form of skin cancer, has undergone a transformative treatment shift with the advent of checkpoint blockade immunotherapy (CBI). Understanding the intricate network of immune cells infiltrating the tumor and orchestrating the control of melanoma cells and the response to CBI is currently of utmost importance. There is evidence underscoring the significance of tissue-resident memory (TRM) CD8 T cells and classic dendritic cell type 1 (cDC1) in cancer protection. Transcriptomic studies also support the existence of a TCF7+ (encoding TCF1) T cell as the most important for immunotherapy response, although uncertainty exists about whether there is a TCF1+TRM T cell due to evidence indicating TCF1 downregulation for tissue residency activation. METHODS: We used multiplexed immunofluorescence and spectral flow cytometry to evaluate TRM CD8 T cells and cDC1 in two melanoma patient cohorts: one immunotherapy-naive and the other receiving immunotherapy. The first cohort was divided between patients free of disease or with metastasis 2 years postdiagnosis while the second between CBI responders and non-responders. RESULTS: Our study identifies two CD8+TRM subsets, TCF1+ and TCF1-, correlating with melanoma protection. TCF1+TRM cells show heightened expression of IFN-γ and Ki67 while TCF1- TRM cells exhibit increased expression of cytotoxic molecules. In metastatic patients, TRM subsets undergo a shift in marker expression, with the TCF1- subset displaying increased expression of exhaustion markers. We observed a close spatial correlation between cDC1s and TRMs, with TCF1+TRM/cDC1 pairs enriched in the stroma and TCF1- TRM/cDC1 pairs in tumor areas. Notably, these TCF1- TRMs express cytotoxic molecules and are associated with apoptotic melanoma cells. Both TCF1+ and TCF1- TRM subsets, alongside cDC1, prove relevant to CBI response. CONCLUSIONS: Our study supports the importance of TRM CD8 T cells and cDC1 in melanoma protection while also highlighting the existence of functionally distinctive TCF1+ and TCF1- TRM subsets, both crucial for melanoma control and CBI response.

Xanthogranulomatous appendicitis; a diagnostic challenge: Clinical Case / Apendicitis xantogranulomatosa; un desafío diagnóstico: Caso Clínico

Introduction: Xanthogranulomatous inflammation is a chronic inflammatory process, rarely located in the appendix. A case of xanthogranulomatous appendicitis is presented. Clinical case. A 77-year-old male presents with intermittent pain in the right hemiabdomen and hyperthermia of one month's evolution. Physical examination showed a tumor in the iliac fossa and right abdomen. He underwent surgery for a probable incarcerated right inguinal hernia, acute perforated appendicitis was found, with inflammation and adhesions, purulent fluid in the right hemiabdomen and abdominal wall dissection. The histopathological result was xanthogranulomatous appendicitis. The evolution of the patient was favorable. Conclusion. Xanthogranulomatous appendicitis simulates a typical picture of acute appendicitis. Histopathologically, pathologies such as Crohn's disease, malacoplakia and tuberculous appendicitis were ruled out.

Introducción. La inflamación xantogranulomatosa es un proceso inflamatorio crónico, rara vez se localiza en apéndice. Se presenta un caso de apendicitis xantogranulomatosa. Caso clínico. Masculino de 77 años, presenta con dolor intermitente en hemiabdomen derecho e hipertermia de un mes de evolución. La exploración física mostró tumoración en fosa iliaca y abdomen derecho. Se sometió a cirugía por probable hernia inguinal derecha incarcerada, se encontró apendicitis aguda perforada, con inflamación y adherencias, líquido purulento en hemiabdomen derecho y disección en pared abdominal. El resultado histopatológico fue apendicitis xantogranulomatosa.  La evolución del paciente fue favorable. Conclusión. La apendicitis xantogranulomatosa simula un cuadro típico de apendicitis aguda. Histopatológicamente se descartan patologías como enfermedad de Crohn, malacoplaquia y apendicitis tuberculosa.