Found 1 Presentation For Request "1476p"
1476P - Immunohistochemical (mIHC) analyses of the immune tumor microenvironment (I-TME) in metastatic renal cell carcinoma (mRCC) patients (pts) receiving immunotherapy: Main results from the Meet-URO 18 study
- Sara Elena Rebuzzi (Genova, Italy)
Abstract
Background
The identification of biomarkers to select pts most likely to benefit from immunotherapy is still an unmet clinical need. The Meet-URO 18 study is a multicenter study assessing the I-TME in mRCC pts treated with ≥2nd line nivolumab divided according to clinical benefit in
Methods
Histology and grading assessment and digital multitarget IHC analyses were performed on the I-TME of the primary tumor or the metastases assessing T-lineage (CD3, CD4, CD8, CD8/CD4 ratio, peritumoral T cells), macrophages (CD68) and granulocytes (CD15). Phosphorylated mTOR (ph-mTOR), CD56 and PD-L1 (SP263) expression on tumor cells were also assessed. Receiver operating curves (ROC) based on responses were used to identify cut-off values of the I-TME parameters. Differences between the two pts groups were reported as odds-ratios (OR) with the 95% CI and considered statistically significant with a p value of < 0.05.
Results
Overall, 116 tumor tissue samples (59% primary tumors, 41% metastases) were evaluated.
Parameter (cut-off) Responders (%) Non responders (%) OR (95% CI), p value (p) CCRCC 62 85 3.57 (1.46-8.71); p=0.005 Other 38 15 ref 1-2 49 20 ref 3 34 51 3.68 (1.30-10.40); p=0.014 4 17 29 4.25 (1.25-14.50); p=0.021 <15 29 49 ref ≥15 71 51 0.42 (0.20-0.91); p=0.029 <70 75 53 ref ≥70 25 47 2.65 (1.21-5.83); p=0.015 <40 73 88 ref ≥40 27 12 0.35 (0.13-0.93); p=0.035
Conclusions
Cancers which benefit from nivolumab are characterized by high expression of CD56 and low levels of regulatory CD4 cells. CCRCC pts have less benefit from nivolumab monotherapy, probably due to rely on tumoral angiogenesis. Linking ph-mTOR and immune response open new cross-road pathways for further investigation. Further gene signature analyses are planned to integrate IHC analyses.
Clinical trial identification
Protocol number: 209/2020 - DB id 10531. Release date: 30/06/2020.
Legal entity responsible for the study
Giuseppe Fornarini.
Funding
Lega Italiana per la Lotta contro i Tumori (LILT), Italian Network For Research In Urologic-Oncology (Meet-URO).
Disclosure
All authors have declared no conflicts of interest.