Insulin receptor expression to predict resistance to axitinib and elucidation of the underlying molecular mechanism in metastatic renal cell carcinoma

Takahashi, Masayuki; Daizumoto, Kei; Fukawa, Tomoya; Fukuhara, Yayoi; Bando, Yoshimi; Kowada, Minoru; Dondoo, Tsogt-Ochir; Sasaki, Yutaro; Tomida, Ryotaro; Ueno, Yoshiteru; Tsuda, Momoko; Kusuhara, Yoshito; Yamaguchi, Kunihisa; Yamamoto, Yoshihiko; Uehara, Hisanori; Kanayama, Hiro‐omi

doi:10.1038/s41416-023-02325-8

Cited by 1 publication

(2 citation statements)

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“…Furthermore, endothelial cells exhibiting decreased INSR levels in RCC can secrete interferon-β, triggering PD-L1 expression and thereby contributing to axitinib resistance (Fig. 4 ) [ 92 ].…”

Section: Role and Regulation Of Pd1/pd-l1 Pathway In Ccrccmentioning

confidence: 99%

“…TAMs can induce an immunosuppressive phenotype in CD4 + T cells by reducing the production of effector cytokines, increasing IL-10 production, and enhancing the expression of co-inhibitory molecules PD-1 and TIM-3 [ 91 ]. Endothelial cells with reduced INSR may contribute to axitinib resistance by secreting interferon-β and inducing PD-L1 expression [ 92 ] …”

Section: Role and Regulation Of Pd1/pd-l1 Pathway In Ccrccmentioning

confidence: 99%

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PD1/PD-L1 blockade in clear cell renal cell carcinoma: mechanistic insights, clinical efficacy, and future perspectives

Zhu,

Jin,

Zhou

et al. 2024

Mol Cancer

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The advent of PD1/PD-L1 inhibitors has significantly transformed the therapeutic landscape for clear cell renal cell carcinoma (ccRCC). This review provides an in-depth analysis of the biological functions and regulatory mechanisms of PD1 and PD-L1 in ccRCC, emphasizing their role in tumor immune evasion. We comprehensively evaluate the clinical efficacy and safety profiles of PD1/PD-L1 inhibitors, such as Nivolumab and Pembrolizumab, through a critical examination of recent clinical trial data. Furthermore, we discuss the challenges posed by resistance mechanisms to these therapies and potential strategies to overcome them. We also explores the synergistic potential of combination therapies, integrating PD1/PD-L1 inhibitors with other immunotherapies, targeted therapies, and conventional modalities such as chemotherapy and radiotherapy. In addition, we examine emerging predictive biomarkers for response to PD1/PD-L1 blockade and biomarkers indicative of resistance, providing a foundation for personalized therapeutic approaches. Finally, we outline future research directions, highlighting the need for novel therapeutic strategies, deeper mechanistic insights, and the development of individualized treatment regimens. Our work summarizes the latest knowledge and progress in this field, aiming to provide a valuable reference for improving clinical efficacy and guiding future research on the application of PD1/PD-L1 inhibitors in ccRCC.

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Section: Role and Regulation Of Pd1/pd-l1 Pathway In Ccrccmentioning

confidence: 99%