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Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Kidney Cancer | Research

Interaction of immune cells with renal cancer development: Mendelian randomization (MR) study

Authors: Zhongwen Lu, Yu Yin, Tian Rao, Xinchi Xu, Kai Zhao, Zhanpeng Liu, Chao Qin, Min Tang

Published in: BMC Cancer | Issue 1/2024

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Abstract

Background

Renal cell carcinoma (RCC) is a prevalent and extensively immune-infiltrated malignancy of the urinary system. Immune cells play a crucial role in both the progression and therapeutic interventions targeting RCC. Nevertheless, the interplay between RCC and immune cells remains understudied, lacking substantial evidence supporting their causal relationship.

Methods

For the purpose of investigating the causal connection between RCC and immune cell characteristics, a two-way two-sample Mendelian randomization (MR) analysis was carried out in this study. The aim was to determine whether specific immune cell traits have a causal impact on the risk of RCC. In order to achieve this, publicly accessible genetic data was utilized to examine and establish the potential relationship between 731 immune cell characteristics and the likelihood of developing RCC. Additionally, various techniques were applied to verify the reliability, variability, and presence of horizontal pleiotropy in the outcomes.

Results

We found a bidirectional causal relationship between RCC and immune cells according to the MR analysis results. It should be noted that CD4-CD8-T cells (OR = 1.61, 95%CI = 1.02–2.55, P = 4.07 × 10–2) pose a risk for RCC, whereas BAFF-R (OR = 0.69, 95%CI = 0.53–0.89, P = 5.74 × 10–3) and CD19 (OR = 0.59, 95%CI = 1.02–2.55, P = 4.07 × 10–2) on B cells act as protective factors. Furthermore, the presence of RCC reduces the levels of B cells (OR = 1.05, 95%CI = 1.01–1.09, P = 1.19 × 10–2) and CD8 + T cells (OR = 1.04, 95%CI = 1.00–1.08, P = 2.83 × 10–2).

Conclusions

Our research illustrates the intricate correlation between immune cells and RCC, presenting novel insights for the prospective safeguarding against RCC risk and the exploration of fresh therapeutic targets.
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Literature
1.
go back to reference Linehan WM, Walther MM, Zbar B. The genetic basis of cancer of the kidney. J Urol. 2003;170(6 Pt 1):2163–72.CrossRefPubMed Linehan WM, Walther MM, Zbar B. The genetic basis of cancer of the kidney. J Urol. 2003;170(6 Pt 1):2163–72.CrossRefPubMed
2.
go back to reference Ljungberg B, et al. European Association of Urology Guidelines on Renal Cell Carcinoma: The 2022 Update. Eur Urol. 2022;82(4):399–410.CrossRefPubMed Ljungberg B, et al. European Association of Urology Guidelines on Renal Cell Carcinoma: The 2022 Update. Eur Urol. 2022;82(4):399–410.CrossRefPubMed
3.
go back to reference Mao W, et al. Current status of research on exosomes in general and for the diagnosis and treatment of kidney cancer in particular. J Exp Clin Cancer Res. 2021;40(1):305.CrossRefPubMedPubMedCentral Mao W, et al. Current status of research on exosomes in general and for the diagnosis and treatment of kidney cancer in particular. J Exp Clin Cancer Res. 2021;40(1):305.CrossRefPubMedPubMedCentral
5.
go back to reference Motzer RJ, Jonasch E, Agarwal N, Alva A, Baine M, Beckermann K, Carlo MI, Choueiri TK, Costello BA, Derweesh IH, Desai A, Ged Y, George S, Gore JL, Haas N, Hancock SL, Kapur P, Kyriakopoulos C, Lam ET, Lara PN, Lau C, Lewis B, Madoff DC, Manley B, Michaelson MD, Mortazavi A, Nandagopal L, Plimack ER, Ponsky L, Ramalingam S, Shuch B, Smith ZL, Sosman J, Dwyer MA, Gurski LA, Motter A. Kidney Cancer, Version 3. 2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017;15(6):804–34.CrossRefPubMed Motzer RJ, Jonasch E, Agarwal N, Alva A, Baine M, Beckermann K, Carlo MI, Choueiri TK, Costello BA, Derweesh IH, Desai A, Ged Y, George S, Gore JL, Haas N, Hancock SL, Kapur P, Kyriakopoulos C, Lam ET, Lara PN, Lau C, Lewis B, Madoff DC, Manley B, Michaelson MD, Mortazavi A, Nandagopal L, Plimack ER, Ponsky L, Ramalingam S, Shuch B, Smith ZL, Sosman J, Dwyer MA, Gurski LA, Motter A. Kidney Cancer, Version 3. 2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017;15(6):804–34.CrossRefPubMed
6.
go back to reference Dai S, et al. Intratumoral CXCL13+CD8+T cell infiltration determines poor clinical outcomes and immunoevasive contexture in patients with clear cell renal cell carcinoma. J Immuno Therapy of Cancer. 2021;9(2):e001823.CrossRef Dai S, et al. Intratumoral CXCL13+CD8+T cell infiltration determines poor clinical outcomes and immunoevasive contexture in patients with clear cell renal cell carcinoma. J Immuno Therapy of Cancer. 2021;9(2):e001823.CrossRef
8.
go back to reference Krishna C, et al. Single-cell sequencing links multiregional immune landscapes and tissue-resident T cells in ccRCC to tumor topology and therapy efficacy. Cancer Cell. 2021;39(5):662–677.e6.CrossRefPubMedPubMedCentral Krishna C, et al. Single-cell sequencing links multiregional immune landscapes and tissue-resident T cells in ccRCC to tumor topology and therapy efficacy. Cancer Cell. 2021;39(5):662–677.e6.CrossRefPubMedPubMedCentral
9.
go back to reference Senbabaoglu Y, et al. Tumor immune microenvironment characterization in clear cell renal cell carcinoma identifies prognostic and immunotherapeutically relevant messenger RNA signatures. Genome Biol. 2016;17(1):231.CrossRefPubMedPubMedCentral Senbabaoglu Y, et al. Tumor immune microenvironment characterization in clear cell renal cell carcinoma identifies prognostic and immunotherapeutically relevant messenger RNA signatures. Genome Biol. 2016;17(1):231.CrossRefPubMedPubMedCentral
10.
go back to reference Kansler ER, et al. Cytotoxic innate lymphoid cells sense cancer cell-expressed interleukin-15 to suppress human and murine malignancies. Nat Immunol. 2022;23(6):904–15.CrossRefPubMedPubMedCentral Kansler ER, et al. Cytotoxic innate lymphoid cells sense cancer cell-expressed interleukin-15 to suppress human and murine malignancies. Nat Immunol. 2022;23(6):904–15.CrossRefPubMedPubMedCentral
11.
13.
14.
16.
go back to reference Wang Z, et al. Association between inflammatory bowel disease and periodontitis: A bidirectional two-sample Mendelian randomization study. J Clin Periodontol. 2023;50(6):736–43.CrossRefPubMed Wang Z, et al. Association between inflammatory bowel disease and periodontitis: A bidirectional two-sample Mendelian randomization study. J Clin Periodontol. 2023;50(6):736–43.CrossRefPubMed
19.
20.
go back to reference Fabiola Del Greco M, Minelli C, Sheehan NA, Thompson JR. Detecting pleiotropy in Mendelian randomisation studies with summary data and a continuous outcome. Stat Med. 2015;34(21):2926–40.CrossRef Fabiola Del Greco M, Minelli C, Sheehan NA, Thompson JR. Detecting pleiotropy in Mendelian randomisation studies with summary data and a continuous outcome. Stat Med. 2015;34(21):2926–40.CrossRef
21.
go back to reference Song J, et al. The causal links between gut microbiota and COVID-19: A Mendelian randomization study. J Med Viro. 2023;95(5):e28784.CrossRef Song J, et al. The causal links between gut microbiota and COVID-19: A Mendelian randomization study. J Med Viro. 2023;95(5):e28784.CrossRef
22.
go back to reference Sharma A, et al. Anti-CTLA-4 Immunotherapy Does Not Deplete FOXP3+ Regulatory T Cells (Tregs) in Human Cancers. Clin Cancer Res. 2019;25(4):1233–8.CrossRefPubMed Sharma A, et al. Anti-CTLA-4 Immunotherapy Does Not Deplete FOXP3+ Regulatory T Cells (Tregs) in Human Cancers. Clin Cancer Res. 2019;25(4):1233–8.CrossRefPubMed
25.
go back to reference Wang Y, et al. Anti-CAIX BBζ CAR4/8 T cells exhibit superior efficacy in a ccRCC mouse model. Molecular Therapy - Oncolytics. 2022;24:385–99.CrossRefPubMed Wang Y, et al. Anti-CAIX BBζ CAR4/8 T cells exhibit superior efficacy in a ccRCC mouse model. Molecular Therapy - Oncolytics. 2022;24:385–99.CrossRefPubMed
28.
go back to reference Reustle A, et al. Integrative-omics and HLA-ligandomics analysis to identify novel drug targets for ccRCC immunotherapy. Genome Medicine. 2020;12(1):32.CrossRefPubMedPubMedCentral Reustle A, et al. Integrative-omics and HLA-ligandomics analysis to identify novel drug targets for ccRCC immunotherapy. Genome Medicine. 2020;12(1):32.CrossRefPubMedPubMedCentral
29.
go back to reference Jacquier A, et al. Tumor infiltrating and peripheral CD4+ILT2+ T cells are a cytotoxic subset selectively inhibited by HLA-G in clear cell renal cell carcinoma patients. Cancer Lett. 2021;519:105–16.CrossRefPubMed Jacquier A, et al. Tumor infiltrating and peripheral CD4+ILT2+ T cells are a cytotoxic subset selectively inhibited by HLA-G in clear cell renal cell carcinoma patients. Cancer Lett. 2021;519:105–16.CrossRefPubMed
30.
go back to reference Tronik-Le Roux D, et al. The HLA-G immune checkpoint: a new immuno-stimulatory role for the α1-domain-deleted isoform. Cell Mol Life Sci. 2022;79(6):310.CrossRefPubMed Tronik-Le Roux D, et al. The HLA-G immune checkpoint: a new immuno-stimulatory role for the α1-domain-deleted isoform. Cell Mol Life Sci. 2022;79(6):310.CrossRefPubMed
32.
go back to reference Dimitrios L, Wagner EF, Michael A, Pulsipher MA, Ahmed N, Mohamad Hamieh M, Hegde M, Ruella M, Savoldo B, Shah NN, Turtle CJ, Wayne AS, Abou-el-Enein A. Immunogenicity of CAR T cells in cancer therapy. Nat Rev Clin Oncol. 2021;18(6):379–93.CrossRef Dimitrios L, Wagner EF, Michael A, Pulsipher MA, Ahmed N, Mohamad Hamieh M, Hegde M, Ruella M, Savoldo B, Shah NN, Turtle CJ, Wayne AS, Abou-el-Enein A. Immunogenicity of CAR T cells in cancer therapy. Nat Rev Clin Oncol. 2021;18(6):379–93.CrossRef
33.
go back to reference Xiuli Wang ZD, Awuah D, Chang WS, Cheng WA, Vyas V, Cha SC, Anderson AJ, Zhang T, Wang Z, Szymura SJ, Kuang BZ, Clark MC, Aldoss I, Forman SJ, Kwak LW, Qin H. CD19/BAFF-R dual-targeted CAR T cells for the treatment of mixed antigennegative variants of acute lymphoblastic leukemia. Leukemia. 2022;36(4):1015–24.CrossRefPubMedPubMedCentral Xiuli Wang ZD, Awuah D, Chang WS, Cheng WA, Vyas V, Cha SC, Anderson AJ, Zhang T, Wang Z, Szymura SJ, Kuang BZ, Clark MC, Aldoss I, Forman SJ, Kwak LW, Qin H. CD19/BAFF-R dual-targeted CAR T cells for the treatment of mixed antigennegative variants of acute lymphoblastic leukemia. Leukemia. 2022;36(4):1015–24.CrossRefPubMedPubMedCentral
35.
go back to reference Manzoni M, et al. Immunological Effects of Bevacizumab-Based Treatment in Metastatic Colorectal Cancer. Oncology. 2011;79(3–4):187–96. Manzoni M, et al. Immunological Effects of Bevacizumab-Based Treatment in Metastatic Colorectal Cancer. Oncology. 2011;79(3–4):187–96.
36.
go back to reference Lebedeva IV, et al. Prediction of novel target genes and pathways involved in bevacizumab-resistant colorectal cancer. Plos One. 2018;13(1):e0189582.CrossRef Lebedeva IV, et al. Prediction of novel target genes and pathways involved in bevacizumab-resistant colorectal cancer. Plos One. 2018;13(1):e0189582.CrossRef
37.
go back to reference Lin Z, et al. Tumor infiltrating CD19+ B lymphocytes predict prognostic and therapeutic benefits in metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors. OncoImmunology. 2018;7(10):1–9.CrossRefPubMedCentral Lin Z, et al. Tumor infiltrating CD19+ B lymphocytes predict prognostic and therapeutic benefits in metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors. OncoImmunology. 2018;7(10):1–9.CrossRefPubMedCentral
Metadata
Title
Interaction of immune cells with renal cancer development: Mendelian randomization (MR) study
Authors
Zhongwen Lu
Yu Yin
Tian Rao
Xinchi Xu
Kai Zhao
Zhanpeng Liu
Chao Qin
Min Tang
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-024-12196-8

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