In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 6_suppl ( 2023-02-20), p. 541-541
Abstract:
541 Background: PURE-01 trial enrolled 155 patients who received 3 cycles of pembrolizumab (IO) every 3 weeks before radical cystectomy. We compared tumor-microenvironment immune markers expression in pre- and post-IO TURB specimens in complete/major and non-responders to identify features associated with pathologic response. Methods: We evaluated pre-IO TURB samples of 18 complete responders (CR: ypT0), 6 major responders (MR: ypTa/ypT1) and 19 non-responders (NR: ypT2/ypT3, N0 or N+) and post-IO specimen of 7 CR, 3 MR and 14 NR. Immunohistochemistry analysis for lymphocytes (CD3, CD8, CD20), macrophages (CD68, CD163), immune checkpoints (PD1, PD-L1) and HLA molecule (MHC-I, HLA-DR, B2M) was performed. A semiquantitative count was made on all samples by 3 expert pathologists and a quantitative whole-slide digital evaluation was performed using QuPath (v.0.3) to assess cell density (cells per mm 2 ) and expression of immune checkpoint and HLA molecules. Results: Semiquantitative count showed that seven markers (CD8, CD163, stromal or tumor PD-L1, HLA-DR and B2M on tumor cells) were significantly more expressed on TURB lesions from responders (CR + MR or CR only) compared to NR (N0 or N+) (p-value range: 0.001 to 0.048). In addition to such markers, patients achieving a CR, compared to NR, showed significantly higher expression of CD68 and CD163, of PD-1 on lymphocytes, as well as of tumor MHC-I molecules. Comparison of lesions from patients with CR vs MR revealed significant differences for CD3, CD163, PD-1 and MHC-I, all these markers being more frequently expressed on the former group compared to the latter. Digital pathology analysis confirmed this results on whole-slide evaluation showing higher density of CD8, CD163, PD-L1 and PD-1, and a higher expression B2M, MHC-I and HLA-DR (p-value range: 0.02 to 0.002) in responders. Moreover, N0 patients showed higher expression of PD-L1 and HLA-DR compared to N+ patients. Comparison of pre- and post-IO samples from NR patients showed an increased density of CD8 and CD20 cells (p-value: 0.04 and 0.01), and a decrease of CD163 and HLA-ABC (p-value: 0.003 and 0.02) expressing cells in the post-therapy samples. Conclusions: The tumor immune microenvironment of pre-therapy TURB lesions of patients achieving a complete or major pathologic response after neoadjuvant pembrolizumab shows significant enrichment for T cells and myeloid cells, for stromal or tumor PD-L1 as well as increased MHC-I expression on tumor cells compared to lesions from non responders. Post-IO surgical samples of NR patients showed downregulation of HLA-Class I antigens, in spite of increased CD8 and CD20 density. Clinical trial information: NCT02736266 .
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2023.41.6_suppl.541
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2023
detail.hit.zdb_id:
2005181-5
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