Characterization of Tumor and Immune Tumor Microenvironment of Primary Tumors and Metastatic Sites in Advanced Renal Cell Carcinoma Patients Based on Response to Nivolumab Immunotherapy: Preliminary Results from the Meet-URO 18 Study.

Autor: Rebuzzi SE; Medical Oncology Unit, Ospedale San Paolo, 17100 Savona, Italy.; Department of Internal Medicine and Medical Specialties (Di.M.I.), University of Genoa, 16132 Genoa, Italy., Brunelli M; Pathology Unit, Department of Diagnostics and Public Health, University and Hospital Trust of Verona, 37124 Verona, Italy., Galuppini F; Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, 35128 Padua, Italy., Vellone VG; Pathology Unit, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy., Signori A; Department of Health Sciences (DISSAL), Section of Biostatistics, University of Genoa, 16132 Genoa, Italy., Catalano F; Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy., Damassi A; Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy., Gaggero G; Pathology Unit, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy., Rescigno P; Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy.; Translational and Clinical Research Institute, Centre for Cancer, Newcastle University, Newcastle upon Tyne NE1 7RU, UK., Maruzzo M; Oncology Unit 1, Istituto Oncologico Veneto IOV-IRCCS, 35128 Padua, Italy., Merler S; Section of Oncology, Department of Medicine, University of Verona and Verona University Hospital Trust, 37134 Verona, Italy., Vignani F; Division of Medical Oncology, Ordine Mauriziano Hospital, 10128 Turin, Italy., Cavo A; Oncology Unit, Villa Scassi Hospital, 16149 Genoa, Italy., Basso U; Oncology Unit 1, Istituto Oncologico Veneto IOV-IRCCS, 35128 Padua, Italy., Milella M; Section of Oncology, Department of Medicine, University of Verona and Verona University Hospital Trust, 37134 Verona, Italy., Panepinto O; Division of Medical Oncology, Ordine Mauriziano Hospital, 10128 Turin, Italy., Mencoboni M; Oncology Unit, Villa Scassi Hospital, 16149 Genoa, Italy., Sbaraglia M; Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, 35128 Padua, Italy., Dei Tos AP; Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, 35128 Padua, Italy., Murianni V; Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy., Cremante M; Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy., Llaja Obispo MA; Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy., Maffezzoli M; Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy., Banna GL; Department of Oncology, Portsmouth Hospitals University NHS Trust, Portsmouth PO6 3LY, UK., Buti S; Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy.; Medical Oncology Unit, University Hospital of Parma, 43126 Parma, Italy., Fornarini G; Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2023 Apr 21; Vol. 15 (8). Date of Electronic Publication: 2023 Apr 21.
DOI: 10.3390/cancers15082394
Abstrakt: Background: Prognostic and predictive factors for patients with metastatic renal cell carcinoma (mRCC) treated with immunotherapy are highly warranted, and the immune tumor microenvironment (I-TME) is under investigation.
Methods: The Meet-URO 18 was a multicentric retrospective study assessing the I-TME in mRCC patients treated with ≥2nd-line nivolumab, dichotomized into responders and non-responders according to progression-free survival (≥12 months and ≤3 months, respectively). The primary objective was to identify differential immunohistochemical (IHC) patterns between the two groups. Lymphocyte infiltration and the expressions of different proteins on tumor cells (CD56, CD15, CD68, and ph-mTOR) were analyzed. The expression of PD-L1 was also assessed.
Results: A total of 116 tumor tissue samples from 84 patients (59% were primary tumors and 41% were metastases) were evaluated. Samples from responders (N = 55) were significantly associated with lower expression of CD4+ T lymphocytes and higher levels of ph-mTOR and CD56+ compared with samples from non-responders (N = 61). Responders also showed a higher CD3+ expression ( p = 0.059) and CD8+/CD4+ ratio ( p = 0.084). Non-responders were significantly associated with a higher percentage of clear cell histology and grading.
Conclusions: Differential IHC patterns between the tumors in patients who were responders and non-responders to nivolumab were identified. Further investigation with genomic analyses is planned.
Databáze: MEDLINE
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