Found 1 Presentation For Request "1476p"

Renal cancer

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

Presentation Number
1476P
Speakers
  • Sara Elena Rebuzzi (Genova, Italy)
Date
Mon, 12.09.2022

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 responders versus non-responders (progression-free survival ≥ 12 vs ≤ 3 months, respectively).

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. Responders (N = 55) presented lower expression of CD4 and higher levels of ph-mTOR and CD56 compared to non responders. Responders showed also a tendency towards higher CD3 expression (≥40: 73% vs 56%, p=0.059) and CD8/CD4 ratio (median 1.74 vs 1.20, p=0.084). Non responders (N = 61) presented with clear cell histology (CCRCC) and higher grading. Statistically significant results are summarized in the table.

Parameter (cut-off) Responders (%) Non responders (%) OR (95% CI), p value (p)
Histology
CCRCC 62 85 3.57 (1.46-8.71); p=0.005
Other 38 15 ref
Grading
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
Ph-mTOR
<15 29 49 ref
≥15 71 51 0.42 (0.20-0.91); p=0.029
CD4
<70 75 53 ref
≥70 25 47 2.65 (1.21-5.83); p=0.015
CD56
<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.

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