Prognostic significance of ATM mutations in chronic lymphocytic leukemia: A meta-analysis

Vaji, Farnaz Baghaei; Nasr, Arash Boroumand; Rezvani, Ali Reza; Ayatollahi, Hossein; Goudarzi, Sajad; Lavasani, Soroush; Bagheri, Ramin Khameneh

doi:10.1016/j.leukres.2021.106729

Leukemia Research

2021

DOI: 10.1016/j.leukres.2021.106729

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Prognostic significance of ATM mutations in chronic lymphocytic leukemia: A meta-analysis

Farnaz Baghaei Vaji

Arash Boroumand Nasr

Ali Reza Rezvani

et al.

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2024

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ATM inhibition enhance immunotherapy by activating STING signaling and augmenting MHC Class I

Li,

Wang,

et al. 2024

Cell Death Dis

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Accumulating evidence supports the concept that DNA damage response targeted therapies can improve antitumor immune response by increasing the immunogenicity of tumor cells and improving the tumor immune microenvironment. Ataxia telangiectasia mutated (ATM) is a core component of the DNA repair system. Although the ATM gene has a significant mutation rate in many human cancers, including colorectal, prostate, lung, and breast, it remains understudied compared with other DDR-involved molecules such as PARP and ATR. Here, we found that either gene knockout or drug intervention, ATM inhibition activated the cGAS/STING pathway and augmented MHC class I in CRC cells, and these effects could be amplified by radiation. Furthermore, we found that MHC class I upregulation induced by ATM inhibition is dependent on the activation of the NFκB/IRF1/NLRC5 pathway and independent of STING. Animal experiments have shown increasing infiltration and cytotoxic function of T cells and better survival in ATM-deficient tumors. This work indicated that ATM nonsense mutation predicted the clinical benefits of radiotherapy combined with immune checkpoint blockade for patients with CRC. It also provides a molecular mechanism rationale for ATM-targeted agents for patients with CRC.

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ATM inhibition enhance immunotherapy by activating STING signaling and augmenting MHC Class I

Li,

Wang,

et al. 2024

Cell Death Dis

View full text Add to dashboard Cite

show abstract

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Prognostic significance of ATM mutations in chronic lymphocytic leukemia: A meta-analysis

Cited by 1 publication

References 25 publications

ATM inhibition enhance immunotherapy by activating STING signaling and augmenting MHC Class I

ATM inhibition enhance immunotherapy by activating STING signaling and augmenting MHC Class I

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