Multimodal predictors for precision immunotherapy

Roelofsen, Lisanne M.; Kaptein, Paulien; Thommen, Daniela S.

doi:10.1016/j.iotech.2022.100071

Cited by 7 publications

(5 citation statements)

References 140 publications

(159 reference statements)

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“…Our results confirmed those from others, suggesting that irAEs might show associations with ICI efficacy ( 12 , 15 , 29 , 30 ). Moreover, pneumonitis has been suggested to be predictive of favorable outcomes in patients receiving anti-PD-1 antibodies ( 12 , 31 ).…”

Section: Discussionsupporting

confidence: 92%

Immune-related adverse events of anti-PD-1 immune checkpoint inhibitors: a single center experience

Sebestyén,

Major,

Bodoki

et al. 2023

Front. Oncol.

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ObjectivesImmune checkpoint inhibitors (ICIs) stimulate antitumor immune responses and, in parallel, they might trigger autoimmune and other immunopathological mechanisms eventually leading to immune-related adverse events (irAE). In our study, we assessed patients with malignancies who underwent anti-PD-1 treatment at the University of Debrecen, Clinical Center.Patients and methodsBetween June 2017 and May 2021, 207 patients started ICI treatment at our university. A total of 157 patients received nivolumab and 50 were treated with pembrolizumab. We looked for factors associated with the development of irAEs. In addition to correlation studies, we performed binary logistic regression analysis to determine, which factors were associated with irAEs. We also performed Forward Likelihood Ratio (LR) analysis to determine independent prognostic factors.ResultsAt the time of data analysis, the mean duration of treatment was 2.03 ± 0.69 years. ROC analysis determined that 9 or more treatment cycles were associated with a significantly higher risk of irAEs. A total of 125 patients received ≥9 treatment cycles. Three times more patients were treated with nivolumab than pembrolizumab. Of the 207 patients, 66 (32%) developed irAEs. Among the 66 patients who developed irAEs, 36 patients (55%) developed one, 23 (35%) developed two, while 7 (10%) developed three irAEs in the same patient. The most common irAEs were thyroid (33 cases), dermatological (25 cases), pneumonia (14 cases) and gastrointestinal complications (13 cases). Patients who developed irAEs received significantly more treatment cycles (21.8 ± 18.7 versus 15.8 ± 17.4; p=0.002) and were younger at the start of treatment (60.7 ± 10.8 versus 63.4 ± 10.1 years; p=0.042) compared to patients without irAEs. Pembrolizumab-treated patients developed more but less severe irAEs compared to those receiving nivolumab.ConclusionICI treatment is very effective, however, irAEs may develop. These irAEs might be related to the number of treatment cycles and the type of treated malignancy.

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Section: Discussionsupporting

confidence: 92%

Immune-related adverse events of anti-PD-1 immune checkpoint inhibitors: a single center experience

Sebestyén,

Major,

Bodoki

et al. 2023

Front. Oncol.

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“…Additionally, higher tumour mutation burden, often described as >10 mutations/Mb, is another marker that recently has been associated with an enhanced response 40. These different indicators of ICI response do not always overlap,41 and their absence does not necessarily imply inferior efficacy of treatment,42 witness this patient’s lack of any of these markers in the context of an ongoing response.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of dual checkpoint inhibitors in a patient with a mixed hepatocellular cholangiocarcinoma

Sucre,

Bullock,

Peters

2024

BMJ Case Rep

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A woman in her 60s was diagnosed with a metastatic, unresectable rare histological type of liver cancer; combined hepatocellular cholangiocarcinoma. She had palliative chemotherapy, initially with gemcitabine and cisplatin, and then with oxaliplatin, L-folinic acid and fluorouracil. Both treatment strategies demonstrated disease progression, and somatic mutation profiling revealed no actionable mutations. The patient was started on immuno-oncology (IO) with nivolumab and ipilimumab, followed by maintenance nivolumab. She has achieved a sustained ongoing partial response since the start of this therapy for at least 12 months. The outcome in this patient is in keeping with the growing evidence of the role that IO agents have in metastatic biliary tract cancer and also serves to highlight their importance in mixed histology liver tumours.

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“…Differences in secretome profile could be used for diagnostic, prognostic, or as predictive biomarker. Changes in secretome profile can also be used for drug assessment [27,28] or could allow identification of new therapeutic targets in treatment resistant patients. The T-MEGA framework also opens broad perspectives for the study of other cancer types and should help better delineating biological features that are specific of the tumoral process.…”

Section: Discussionmentioning

confidence: 99%

Definition of a novel breast tumor-specific classifier based on secretome analysis

et al. 2022

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Background During cancer development, the normal tissue microenvironment is shaped by tumorigenic events. Inflammatory mediators and immune cells play a key role during this process. However, which molecular features most specifically characterize the malignant tissue remains poorly explored. Methods Within our institutional tumor microenvironment global analysis (T-MEGA) program, we set a prospective cohort of 422 untreated breast cancer patients. We established a dedicated pipeline to generate supernatants from tumor and juxta-tumor tissue explants and quantify 55 soluble molecules using Luminex or MSD. Those analytes belonged to five molecular families: chemokines, cytokines, growth factors, metalloproteinases, and adipokines. Results When looking at tissue specificity, our dataset revealed some breast tumor-specific characteristics, as IL-16, as well as some juxta-tumor-specific secreted molecules, as IL-33. Unsupervised clustering analysis identified groups of molecules that were specific to the breast tumor tissue and displayed a similar secretion behavior. We identified a tumor-specific cluster composed of nine molecules that were secreted fourteen times more in the tumor supernatants than the corresponding juxta-tumor supernatants. This cluster contained, among others, CCL17, CCL22, and CXCL9 and TGF-β1, 2, and 3. The systematic comparison of tumor and juxta-tumor secretome data allowed us to mathematically formalize a novel breast cancer signature composed of 14 molecules that segregated tumors from juxta-tumors, with a sensitivity of 96.8% and a specificity of 96%. Conclusions Our study provides the first breast tumor-specific classifier computed on breast tissue-derived secretome data. Moreover, our T-MEGA cohort dataset is a freely accessible resource to the biomedical community to help advancing scientific knowledge on breast cancer.

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Multimodal predictors for precision immunotherapy

Cited by 7 publications

References 140 publications

Immune-related adverse events of anti-PD-1 immune checkpoint inhibitors: a single center experience

Immune-related adverse events of anti-PD-1 immune checkpoint inhibitors: a single center experience

Efficacy of dual checkpoint inhibitors in a patient with a mixed hepatocellular cholangiocarcinoma

Definition of a novel breast tumor-specific classifier based on secretome analysis

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