Abstract 2142
Background
Renal cell carcinoma (RCC) is considered an immunogenic cancer with a high frequency of indel mutations, immuno-oncological (IO) sensitivity, and infiltration of T cells. Because natural killer (NK) cells are a lesser known population compared to their T cell counterparts, we aimed to investigate the intratumoral phenotype of the cells to assess the overall immune landscape of RCC.
Methods
The tumor, matching peripheral blood (PB) and healthy kidney tissue samples were obtained from 40 RCC patients that underwent radical nephrectomy and were phenotyped using multi-parameter flow cytometry and a comprehensive immunostaining panel containing 56 fundamental markers to cancer immunology.
Results
Using hierarchical clustering and correlation analysis, we discovered that our cohort clustered into two distinct subgroups defined by the abundance of NK cells from the intratumoral lymphocyte population, defined as NKhigh (n = 17; mean 24.3%) and NKlow (n = 18; mean 7.5%). Consequently, an increased abundance of NK cells correlated with a lower expression of PD-1, particularly in the CD8+ T cells (r=-0.5722, p = 0.0003), but not with LAG-3. Contrastingly, clinical parameters such as tumor grade, gender and age did not differ between the two NK subgroups. However, patients with high NK cell abundance significantly had more often necrosis present in the tumors (p = 0.04). We also independently phenotyped two regions of the same tumor sample (n = 10) to compare the periphery and core lymphocytes. Surprisingly, both spatially different regions displayed similar quantities of immune cell populations and immunophenotypic markers. Overall, the tumor immune landscape in RCC resulted in a proportion of tumors carrying a higher abundance of NK cells than their T cell-rich corresponding PB and healthy tissue samples, which supports our findings that a proportion of tumors accumulate NK cells.
Conclusions
Our study has led to the discovery of two distinct RCC tumoral NK cell subgroups, NKhigh and NKlow. Next, we aim to further explore the transcriptional differences of the two subgroups with ongoing bulk RNA sequencing (RNAseq). Furthermore, prospective single-cell RNA sequencing (sc-RNAseq) will be carried out to investigate the immunological heterogeneities in higher resolution.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
University of Helsinki, Hematology Research Unit Helsinki.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5544 - Evaluation of a radiomic signature of CD8 cells in patients treated with immunotherapy-radiotherapy in three clinical trials.
Presenter: Roger Sun
Session: Poster Display session 3
Resources:
Abstract
1117 - Biomarkers predictive of overall survival in advanced cancer patients treated with a peptide-based cancer vaccine.
Presenter: Shigetaka Suekane
Session: Poster Display session 3
Resources:
Abstract
1922 - Expression of PD-L1 in plasma exosomes of NSCLC patients and its associations with PD-L1 expression of corresponding tumor tissues
Presenter: Shaorong Yu
Session: Poster Display session 3
Resources:
Abstract
5495 - Patient’s perspective on digital biomarkers in advanced urologic malignancies
Presenter: Severin Rodler
Session: Poster Display session 3
Resources:
Abstract
3166 - A comprehensive Pan-cancer study of FGFR Aberrations in Chinese cancer patients
Presenter: Yang Gao
Session: Poster Display session 3
Resources:
Abstract
3277 - A Systemic Inflammation Response Index (SIRI) correlates with survival and could be a Predictive Factor for mFOLFIRINOX in Metastatic Pancreatic Cancer (PC)
Presenter: Vilma Pacheco-Barcia
Session: Poster Display session 3
Resources:
Abstract
2680 - Circulating biomarkers and risk of immune-related adverse events (irAEs) in patients (pts) with advanced Non-small cell lung cancer (aNSCLC) and metastatic melanoma (mMel)
Presenter: Alberto Pavan
Session: Poster Display session 3
Resources:
Abstract
4066 - Breast cancer in young women of Kazakh population depending on germline mutations: results of next-generation sequencing
Presenter: Dilyara Kaidarova
Session: Poster Display session 3
Resources:
Abstract
5514 - Discovery of an ImmunoTranscriptomics signature in blood for early colorectal cancer detection
Presenter: Paolo Angelino
Session: Poster Display session 3
Resources:
Abstract
1595 - Serum Netrin-1 as a Biomarker for Colorectal Cancer Detection
Presenter: Jinzhou Zhu
Session: Poster Display session 3
Resources:
Abstract