Inhibition of hyperprogressive cancer disease induced by immune-checkpoint blockade upon co-treatment with meta-tyrosine and p38 pathway inhibitor

Montagna, Daniela; Duarte, Alejandra; Chiarella, Paula; Rearte, Bárbara; Bustuoabad, Oscar D.; Vermeulen, Mónica; Ruggiero, Raúl A.

doi:10.1186/s12885-022-09941-2

Cited by 3 publications

(1 citation statement)

References 48 publications

(86 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Percentage and uorescence of individual cells was measured in a ow cytometer (Becton Dickinson) and were analyzed by Flowing (Software version 2.5.1, Turku Centre for Biotechnology. University of Turku, Finland) (17,19).…”

Section: -Flow Cytometrymentioning

confidence: 99%

Different susceptibility to the development of hepatocellular carcinoma induced by diethylnitrosamine in female and male C3H mice

Montagna

Todero

Postma

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Histopathological features of hepatocellular carcinoma (HCC) induced by diethylnitrosamine (DEN) in mice displays strong similarities with those seen in humans, including the higher tumor prevalence in males than in females. Previous studies have demonstrated that continual production of the pro-inflammatory IL-6 by Kupffer cells is involved in the initiation and progression of DEN-induced HCC and that estrogen-mediated reduction of IL-6 secretion would decrease its incidence in females. However, the mechanisms by which different IL-6 concentrations affect tumor growth are not entirely understood. In this model, we demonstrated that the increased tumor growth observed in males accompanied significant liver damage and larger chronic inflammatory areas. Most tumors were placed into or close to senescent areas (detected by expression of β-galactosidase), and these areas were more extensive in DEN-treated males than in similarly-treated female mice. Further, different markers of systemic and regional immunosuppression (such as neutrophil-to-lymphocyte ratio, PD-1 expression in CD8 T cells, number of PD-L1 + myeloid-derived suppressor cells, etc.) were significantly higher in males than in females from the time the tumors started their exponential growth, suggesting that immunosuppressive mechanisms could contribute to the accelerated tumor growth observed in males. The relationship between chronic inflammation and immunosuppression has been previously documented. In contrast, little is known about the link between senescence and immunosuppression, raising the possibility that senescence may contribute to tumor growth by mechanisms other than immunological. Comparative studies between susceptible and resistant hosts to chemical carcinogenesis may help to unveil novel therapeutic strategies against cancer.

show abstract

Section: -Flow Cytometrymentioning

confidence: 99%

Different susceptibility to the development of hepatocellular carcinoma induced by diethylnitrosamine in female and male C3H mice

Montagna

Todero

Postma

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Prediction model for hyperprogressive disease in patients with advanced solid tumors received immune-checkpoint inhibitors: a pan-cancer study

Long,

Yang,

Bai

et al. 2023

Cancer Cell Int

View full text Add to dashboard Cite

Background Hyper progressive disease (HPD) describes the phenomenon that patients can’t benefit from immunotherapy but cause rapid tumor progression. HPD is a particular phenomenon in immunotherapy but lacks prediction methods. Our study aims to screen the factors that may forecast HPD and provide a predictive model for risky stratifying. Methods We retrospectively reviewed advanced-stage tumor patients who received immune checkpoint inhibitors (ICI) in the General PLA Hospital. Subsequently, we calculated the tumor growth kinetics ratio (TGKr) and identified typical HPD patients. Differences analysis of clinical characteristics was performed, and a predictive binary classification model was constructed. Results 867 patients with complete image information were screened from more than 3000 patients who received ICI between January 2015 and January 2020. Among them, 36 patients were identified as HPD for TGKr > 2. After the propensity score matched, confounding factors were limited. Survival analysis revealed that the clinical outcome of HPD patients was significantly worse than non-HPD patients. Besides, we found that Body Mass Index (BMI), anemia, lymph node metastasis in non-draining areas, pancreatic metastasis, and whether combined with anti-angiogenesis or chemotherapy therapy were closely connected with the HPD incidence. Based on these risk factors, we constructed a visualised predicted nomogram model, and the Area Under Curve (AUC) is 0.850 in the train dataset, whereas 0.812 in the test dataset. Conclusion We carried out a retrospective study for HPD based on real-world patients and constructed a clinically feasible and practical model for predicting HPD incidence, which could help oncologists to stratify risky patients and select treatment strategies.

show abstract

Advances in the Study of Hyperprogression of Different Tumors Treated with PD-1/PD-L1 Antibody and the Mechanisms of Its Occurrence

Zheng

Zhou

et al. 2023

Cancers

View full text Add to dashboard Cite

Immune checkpoint inhibitors (ICIs) including PD-1/PD-L1 antibodies, have demonstrated significant clinical benefits in the treatment of individuals with many types of cancer. However, as more and more patients use such therapies, the side effects of immune checkpoint inhibitors have also been discovered. These include accelerated tumor growth in some patients, creating new lesions, and even life-threatening ones. These side effects are known as hyperprogression disease (HPD), and different types of tumors have different HPD conditions after ICIs treatment. Therefore, understanding the pathogenesis of HPD and predicting its occurrence is critical for patients using ICIs therapy. Here, we will briefly review the current status of PD-1/PD-L1 antibody therapy, HPD occurrence in various types of tumors, and the underlying mechanism.

show abstract

Inhibition of hyperprogressive cancer disease induced by immune-checkpoint blockade upon co-treatment with meta-tyrosine and p38 pathway inhibitor

Cited by 3 publications

References 48 publications

Different susceptibility to the development of hepatocellular carcinoma induced by diethylnitrosamine in female and male C3H mice

Different susceptibility to the development of hepatocellular carcinoma induced by diethylnitrosamine in female and male C3H mice

Prediction model for hyperprogressive disease in patients with advanced solid tumors received immune-checkpoint inhibitors: a pan-cancer study

Advances in the Study of Hyperprogression of Different Tumors Treated with PD-1/PD-L1 Antibody and the Mechanisms of Its Occurrence

Contact Info

Product

Resources

About