Exploration of the immunogenetic landscape of hyperprogressive disease after combined immunotherapy in cancer patients

Gong, Caifeng; Zhang, Wen; Sun, Yangying; Shou, Jianzhong; Jiang, Zhichao; Liu, Tianyi; Wang, Shengzhou; Li, Jun; Yin, Sun; Zhou, Aiping

doi:10.1016/j.isci.2023.106720

Cited by 3 publications

(2 citation statements)

References 32 publications

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“…Genomic profiling emerges as a promising avenue for discerning HP disease, as evidenced by a case report study implicating EGFR alteration and MDM2 amplification as potential indicators for HPD in NSCLC) ( 90 , 91 ). Notably, MDM2/MDM4 amplification was universally detected in all hyper progressive patients, all experiencing cessation of immunotherapy merely two months post-treatment initiation.…”

Section: Hyper Progressive Diseasementioning

confidence: 99%

Further knowledge and developments in resistance mechanisms to immune checkpoint inhibitors

Berland,

Gabr,

Chang

et al. 2024

Front. Immunol.

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The past decade has witnessed a revolution in cancer treatment, shifting from conventional drugs (chemotherapies) towards targeted molecular therapies and immune-based therapies, in particular immune-checkpoint inhibitors (ICIs). These immunotherapies release the host’s immune system against the tumor and have shown unprecedented durable remission for patients with cancers that were thought incurable, such as metastatic melanoma, metastatic renal cell carcinoma (RCC), microsatellite instability (MSI) high colorectal cancer and late stages of non-small cell lung cancer (NSCLC). However, about 80% of the patients fail to respond to these immunotherapies and are therefore left with other less effective and potentially toxic treatments. Identifying and understanding the mechanisms that enable cancerous cells to adapt to and eventually overcome therapy can help circumvent resistance and improve treatment. In this review, we describe the recent discoveries on the onco-immunological processes which govern the tumor microenvironment and their impact on the resistance to PD-1/PD-L1 checkpoint blockade.

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Section: Hyper Progressive Diseasementioning

confidence: 99%

Further knowledge and developments in resistance mechanisms to immune checkpoint inhibitors

Berland,

Gabr,

Chang

et al. 2024

Front. Immunol.

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“…Several studies have indicated that HPD is associated with various factors, including older age, poor performance status, higher tumor burden, as well as amplification of EGFR or MDM2/4, and immune-cell biomarkers. 6 It is worth noting that patients older than 65 are more susceptible to developing HPD, and those with poor performance status (PS) are at a higher risk. 7 , 8 The mechanism connecting HPD and advanced age may be due to the immunosenescence, which causes a reduction generated by age-related thymic atrophy.…”

Section: Introductionmentioning

confidence: 99%

Exploration of genetic characterization in hyperprogressive disease after immunotherapy retreatment in a patient with LCNEC: A case report

Zhang,

Yang,

Shao

et al. 2024

Human Vaccines & Immunotherapeutics

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Immune checkpoint inhibitors (ICIs) have emerged as a promising therapeutic option for large cell neuroendocrine carcinoma (LCNEC). However, various studies have suggested a potential risk of hyperprogressive disease (HPD) in patients receiving ICI, which might be associated with gene alterations. Here, this is the first report on an unknown primary LCNEC patient who had achieved a long-term response from ICI treatment (atezolizumab), but developed HPD after tumor progression due to receiving another ICI agent (serplulimab). The mutation region of FAT4, SMARCA4, CYLD, CTNNB1, and KIT was altered prior to serplulimab treatment compared to before atezolizumab treatment. This case suggested a potential association between these mutated genes and HPD. Patients with the aforementioned genes should caution when selecting ICI treatment. These findings required further confirmation in a larger study cohort.

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Neutrophil-to-lymphocyte ratio as a predictive biomarker for hyperprogressive disease mediated by immune checkpoint inhibitors: a systematic review and meta-analysis

Pei,

Zhang,

Lai

et al. 2024

Front. Immunol.

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BackgroundHyperprogressive disease (HPD) is a novel pattern of paradoxically rapid tumor progression, which often leads to early death, mostly in the first 2 months of treatment with immune checkpoint inhibitors (ICIs). Currently, there is no validated biomarker to assess patients at risk of HPD.AimThe aim of this study was to systematically evaluate the predictive value of the neutrophil-to-lymphocyte ratio (NLR) in HPD and establish a reliable variable to support clinicians in defining personalized treatment strategies.MethodsPubMed, Embase, Web of Science, Scopus, and Cochrane Library databases were searched for studies published before 31 December 2023. The Newcastle–Ottawa Scale (NOS) was used to evaluate the quality of eligible studies. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects or a fixed-effects model to evaluate the association between the NLR and the risk of HPD.ResultsA total of 17 studies with 2,964 patients were included for meta-analysis. The incidence of HPD across different types of tumors ranged from 6.3% to 35.6%. In the pooled analysis of the NLR and HPD, we identified that the NLR significantly associated with the risk of HPD (OR = 0.65; 95% CI: 0.46 to 0.91; p = 0.01) (I2 = 52%, p = 0.007).ConclusionIn the future, the NLR may serve as a remarkable biomarker for predicting the risk of HPD in clinical practice.

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Exploration of the immunogenetic landscape of hyperprogressive disease after combined immunotherapy in cancer patients

Cited by 3 publications

References 32 publications

Further knowledge and developments in resistance mechanisms to immune checkpoint inhibitors

Further knowledge and developments in resistance mechanisms to immune checkpoint inhibitors

Exploration of genetic characterization in hyperprogressive disease after immunotherapy retreatment in a patient with LCNEC: A case report

Neutrophil-to-lymphocyte ratio as a predictive biomarker for hyperprogressive disease mediated by immune checkpoint inhibitors: a systematic review and meta-analysis

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