Background Here, we describe the potential of measuring dynamic changes occurring in peripheral blood as indicators of response to NIVO in mRCC pts. Methods After failure to antiangiogenics, mRCC pts (n=60) received NIVO within the I-RENE trial (NCT04891055). Blood samples were collected during NIVO at baseline, 2, 4, 12 weeks (wks) and at PD. Therapy induced dynamic changes were evaluated in PBMCs and plasma, by high resolution flow cytometry (n=144 lymphoid and myeloid cell subsets) and multiplex analysis, respectively. A panel of very good (n=17, R) and very poor (n=16, NR) responders were selected for correlations. Tumor transcriptomics and immune infiltrate assessment were performed on baseline biopsy to gain insight into the immunomodulation occurring at tumor site. Results Dynamic changes were detected in multiple PBMC subsets and plasma cyto/chemokines since 2 wks from NIVO and at subsequent time points in all pts. However, R pts showed at 2 wks a statistically significant decrease of monocytic MDSCs (M-MDSC, CD14+HLA-DRneg) cells, followed at 4 wks by a boost of CD8+ and central memory T cells, and reduction of CD38+ T cells. At 12 wks CD14+HLA-DRneg MDSCs reached the lowest peripheral blood level without further changes in the lymphoid cell subsets. At opposite, NR pts showed a progressive increase of M-MDSCs and inflammatory/immunosuppressive monocytes (CD14+PD-L1+), associated at 12 wks with a significant upregulation of senescent (KLRG1+CD28-CD57+) CD8+ T cells and CD38+ T cells. Nivo induced a decrease of plasma IL-8, Pentraxin 3, PCSIK9 and miR-125b, and an increase of VEGFR2, all of which were associated with good response at 12 wks. Integration of PBIP with tumor tissue results will pair systemic immunomodulations with tumor microenvironment. Conclusions Specific kinetics of immunosuppressive myeloid cell subsets versus memory/effector T cells early during NIVO associate with outcome. Combining dynamic peripheral blood variables with clinical information may give rise to novel biomarkers for tailored therapeutic decision-making in mRCC pts.
1901P Specific dynamic changes of peripheral blood immune profile (PBIP) associate with clinical response to nivolumab (NIVO) in patients (pts) with metastatic renal cell carcinoma (mRCC): The I-RENE trial (meet-URO 8) / Verzoni, E.; Procopio, G.; Bottiglieri, A.; Stellato, M.; Rametta, A.; Zucali, P. A.; Perrucci, B.; G. fornarini, Null; Buti, S.; Maruzzo, M.; Cova, A.; Squarcina, P.; Lalli, L.; Mereu, A.; Cerioli, N.; Agnelli, L.; Todoerti, K.; Busico, A.; Rivoltini, L.; Huber, V.. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - 34:(2023), pp. S1022-S1023. [10.1016/j.annonc.2023.09.1131]
1901P Specific dynamic changes of peripheral blood immune profile (PBIP) associate with clinical response to nivolumab (NIVO) in patients (pts) with metastatic renal cell carcinoma (mRCC): The I-RENE trial (meet-URO 8)
Buti, S.Investigation
;
2023-01-01
Abstract
Background Here, we describe the potential of measuring dynamic changes occurring in peripheral blood as indicators of response to NIVO in mRCC pts. Methods After failure to antiangiogenics, mRCC pts (n=60) received NIVO within the I-RENE trial (NCT04891055). Blood samples were collected during NIVO at baseline, 2, 4, 12 weeks (wks) and at PD. Therapy induced dynamic changes were evaluated in PBMCs and plasma, by high resolution flow cytometry (n=144 lymphoid and myeloid cell subsets) and multiplex analysis, respectively. A panel of very good (n=17, R) and very poor (n=16, NR) responders were selected for correlations. Tumor transcriptomics and immune infiltrate assessment were performed on baseline biopsy to gain insight into the immunomodulation occurring at tumor site. Results Dynamic changes were detected in multiple PBMC subsets and plasma cyto/chemokines since 2 wks from NIVO and at subsequent time points in all pts. However, R pts showed at 2 wks a statistically significant decrease of monocytic MDSCs (M-MDSC, CD14+HLA-DRneg) cells, followed at 4 wks by a boost of CD8+ and central memory T cells, and reduction of CD38+ T cells. At 12 wks CD14+HLA-DRneg MDSCs reached the lowest peripheral blood level without further changes in the lymphoid cell subsets. At opposite, NR pts showed a progressive increase of M-MDSCs and inflammatory/immunosuppressive monocytes (CD14+PD-L1+), associated at 12 wks with a significant upregulation of senescent (KLRG1+CD28-CD57+) CD8+ T cells and CD38+ T cells. Nivo induced a decrease of plasma IL-8, Pentraxin 3, PCSIK9 and miR-125b, and an increase of VEGFR2, all of which were associated with good response at 12 wks. Integration of PBIP with tumor tissue results will pair systemic immunomodulations with tumor microenvironment. Conclusions Specific kinetics of immunosuppressive myeloid cell subsets versus memory/effector T cells early during NIVO associate with outcome. Combining dynamic peripheral blood variables with clinical information may give rise to novel biomarkers for tailored therapeutic decision-making in mRCC pts.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
