Angiogenesis Inhibitors and Immunomodulation in Renal Cell Cancers: The Past, Present, and Future

Kasherman, Lawrence; Siu, Derrick Ho Wai; Woodford, Rachel; Harris, Carole A.

doi:10.3390/cancers14061406

Cited by 18 publications

(17 citation statements)

References 123 publications

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“…Asterisk represents significant differential ECAR value between LRNF1 overexpression group and negative control group, as well as between LRNF1 overexpression group and LRFN1 + mimics group using unpaired t test (P < 0.05). *P < 0.05; ***P < 0.001; ****P < 0.0001 from different perspectives will help to deepen the understanding of the interaction between tumor cells and TME, thereby improving the overall efficacy of renal cancer treatment [44,45]. Considering that a large number of lymphocyte infiltration led by CD8 + T cells and the general increase of immune checkpoint molecules are in the LRFN1 high group, and this phenomenon is specific in RCC, this study demonstrated that LRNF1 may affect glycolytic effects of ccRCC cells to evade immune surveillance [46], and thus mediating the immune-infiltrating TIME in ccRCC.…”

Section: Discussionmentioning

confidence: 99%

Deciphering the role of miR-187-3p/LRFN1 axis in modulating progression, aerobic glycolysis and immune microenvironment of clear cell renal cell carcinoma

Liu

Anwaier

et al. 2022

Discov Onc

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Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant genitourinary cancers with high recurrence risk worldwide. Recently, multi-omics data facilitate obtaining a molecular landscape of tumor development, and were implemented to affect pathogenesis, phenotype, and prognosis of ccRCC. In this study, after screening for differential expressed microRNAs based on multiply datasets, we tested expression levels and prognostic value of miR-187-3p in ccRCC samples, and transfected miR-187-3p mimics or negative controls into ccRCC cells. Up-regulation of miR-187-3p restrains proliferation, migration and promotes apoptosis ability in human ccRCC A498 and 786O cells. In addition, Luciferase reporter assay revealed that miR-187-3p directly targets LRFN1-3’-UTR and negatively modulates LRFN1 expression. LRFN1 rescues proliferation and invasion capacities after miR-187-3p mimic transfection in vitro and in subcutaneous xenograft models. We further performed deep-sequencing technology and bioinformatics analyses to evaluate the biological functions and potential clinical implications of LRFN1 expression in ccRCC. Interestingly, LRFN1 could serve as an independent and potential biomarker for prognosis in over 1000 patients with ccRCC from multiply independent cohorts. Besides, the up-regulated LRFN1 expression prominently promoted intra-tumoral heterogeneity and immune-infiltrating microenvironment, represented by elevated M2 macrophage infiltration, CD8+ T cells activity and PD-L1 expression. In conclusion, this study revealed the tumor-specific and immunological role of miR-187-3p/LRFN1 axis in the progression and reshaping of tumor immune microenvironment of ccRCC.

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Section: Discussionmentioning

confidence: 99%

Deciphering the role of miR-187-3p/LRFN1 axis in modulating progression, aerobic glycolysis and immune microenvironment of clear cell renal cell carcinoma

Liu

Anwaier

et al. 2022

Discov Onc

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“…Indeed, renal cancer is also one of the most immunogenic cancers with a tumour microenvironment (TME) characterized by an infiltration of various immune cells with an immunosuppressive phenotype [ 11 ]. Considering the link between angiogenesis and anti-tumour immunity, there is a strong rationale to combine ICI (anti-PD-1) with anti-angiogenic TKI [ 12 ]. Four combinations are currently approved for first-line treatment in m ccRCC (3 TKI-ICI-axitinib plus pembrolizumab, cabozantinib plus nivolumab and lenvatinib plus pembrolizumab—and 1 ICI-ICI-nivolumab plus ipilimumab) [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Renal Carcinoma and Angiogenesis: Therapeutic Target and Biomarkers of Response in Current Therapies

Guillaume

Auvray

Vano

et al. 2022

Cancers

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Due to the aberrant hypervascularization and the high immune infiltration of renal tumours, current therapeutic regimens of renal cell carcinoma (RCC) target angiogenic or immunosuppressive pathways or both. Tumour angiogenesis plays an essential role in tumour growth and immunosuppression. Indeed, the aberrant vasculature promotes hypoxia and can also exert immunosuppressive functions. In addition, pro-angiogenic factors, including VEGF-A, have an immunosuppressive action on immune cells. Despite the progress of treatments in RCC, there are still non responders or acquired resistance. Currently, no biomarkers are used in clinical practice to guide the choice between the different available treatments. Considering the role of angiogenesis in RCC, angiogenesis-related markers are interesting candidates. They have been studied in the response to antiangiogenic drugs (AA) and show interest in predicting the response. They have been less studied in immunotherapy alone or combined with AA. In this review, we will discuss the role of angiogenesis in tumour growth and immune escape and the place of angiogenesis-targeted biomarkers to predict response to current therapies in RCC.

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“…Renal cell carcinoma (RCC) is one of the fastest-growing malignancies worldwide and has more than doubled its incidence in the past decades [ 1 ]. It is the ninth most common malignancy and accounts for more than 13,000 deaths in the United States annually [ 1 , 2 ]. Since 2015, immune checkpoint inhibitors (ICIs) have changed the therapeutic landscape of RCC [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Adding Cyclooxygenase Inhibitors to Immune Checkpoint Inhibitors Did Not Improve Outcomes in Metastatic Renal Cell Carcinoma

Zhang

Kumar

Adashek

et al. 2022

Cells

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Modulating the cyclooxygenase 2 (COX-2) pathway has improved responses to immune checkpoint inhibitors (ICIs) in certain solid tumors, such as melanoma. Little is known about COX-2 inhibition in response to ICIs in metastatic renal cell carcinoma (mRCC). In this retrospective cohort study, we examined the effect of COX-2 inhibitors on the long-term outcomes of mRCC patients undergoing ICI therapies. Among 211 patients with mRCC, 23 patients were excluded due to loss to follow-up. Among 188 included patients, 120 patients received either an NSAID or aspirin for at least three weeks during ICI therapies. Clear cell histology was present in 96% of cases. The median overall survival (OS) was similar regardless of the COX inhibitor (COXi) (i.e., NSAID or aspirin) use (27 months for COXi vs. 33 months for no-COXi groups; p = 0.73). The no-COXi group showed a trend toward longer median progression-free survival (8 months for COXi vs. 13 months for no-COXi groups; p = 0.13). When looking specifically at NSAID use in a multivariate analysis, NSAID use was associated with a higher risk of progression (HR = 1.52 [95% CI, 1.04–2.22]) and death (HR = 1.60 [95% CI, 1.02–2.52]). In summary, COXis did not improve disease control or survival among patients with mRCC who were undergoing ICI therapies. Instead, the concurrent use of NSAIDs was associated with worse outcomes. Larger studies are needed to validate our observation.

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Angiogenesis Inhibitors and Immunomodulation in Renal Cell Cancers: The Past, Present, and Future

Cited by 18 publications

References 123 publications

Deciphering the role of miR-187-3p/LRFN1 axis in modulating progression, aerobic glycolysis and immune microenvironment of clear cell renal cell carcinoma

Deciphering the role of miR-187-3p/LRFN1 axis in modulating progression, aerobic glycolysis and immune microenvironment of clear cell renal cell carcinoma

Renal Carcinoma and Angiogenesis: Therapeutic Target and Biomarkers of Response in Current Therapies

Adding Cyclooxygenase Inhibitors to Immune Checkpoint Inhibitors Did Not Improve Outcomes in Metastatic Renal Cell Carcinoma

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