Correlations between tumor-infiltrating and circulating lymphocyte subpopulations in mRCC patients treated with immune-checkpoint inhibitors

Autor: Nicoletta Campanini, Maricla Galetti, Sebastiano Buti, Lorena Bottarelli, Agnese Cosenza, Leonarda Ferri, Monia Incerti, Francesco Leonardi, Cinzia Azzoni, Melissa Bersanelli, Letizia Gnetti, Enrico Maria Silini, Giuseppe Caruso, Raffaele Parziale, Nicola Sverzellati, Augusto Vaglio, Michele Corrado, Elena Rapacchi, Elena Varotti
Rok vydání: 2017
Předmět:
Zdroj: Journal of Clinical Oncology. 35:494-494
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2017.35.6_suppl.494
Popis: 494 Background: In clinical trials with immune-checkpoint inhibitors (CKI), histological features such as tumor-infiltrating lymphocites (TILs) are investigated as potential predictive biomarkers, with the possible limit of an outdated parameter for a typically dynamic element. Methods: This explorative study compared, in metastatic renal cell carcinoma (mRCC) patients, basal pathological data about TILs on diagnostic histological specimens with circulating lymphocyte subpopulations measured before and during therapy with nivolumab, with the primary aim to assess their concordance. Secondarily, with the limit of a small sample size, a possible relation with treatment outcome was explored. Results: Of 11 mRCC patients, 5 had low presence of TILs (L-TILs), 3 moderate amount (M-TILs), and 3 high number (H-TILs). Overall, 8 patients had low intratumoral pathological CD4+/CD8+ ratio (LIPR) ≤ 1 and 3 cases high intratumoral pathological ratio (HIPR) ≥ 2. Of 8 patients with LIPR, only 2 cases matched with low circulating CD4+/CD8+ ratio (LCR) ≤1, whilst 5 cases had high circulating ratio (HCR) ≥ 2 (1 undetermined). All 3 cases with HIPR (≥ 2) conversely had LCR (≤ 1). Unexpectedly, independently from the clinical outcome, circulating CD4+/CD8+ ratio remained unchanged during therapy with CKI in each patient, maintaining the same value after 8 weeks (mean -0.12). The respective percentage values of CD4+ and CD8+ circulating T cells also remained stable during treatment (mean variation 0%); the absolute value of CD4+ was more likely to increase (mean +46.3/mm3); the level of CD8+ tended to slightly decrease (mean -6.5/mm3). No correlation of lymphocyte subpopulations with treatment outcome was found. Conclusions: Of note, this study did not evidence any correspondence between histopathological and circulating findings in terms of T-lymphocyte subpopulations in mRCC patients undergoing treatment with CKI, also suggesting the inconsistency of circulating data in terms of relative variations. Considering the likely high dynamism of TILs, rebiopsy before CKI therapy might be the most reliable way to assess the utility of TILs characterization for predictive purpose.
Databáze: OpenAIRE
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