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Immuno-Imaging to Predict Treatment Response in Infection, Inflammation and Oncology.

ABSTRACT: BACKGROUND:Molecular nuclear medicine plays a pivotal role for diagnosis in a preclinical phase, in genetically susceptible patients, for radio-guided surgery, for disease relapse evaluation, and for therapy decision-making and follow-up. This is possible thanks to the development of new radiopharmaceuticals to target specific biomarkers of infection, inflammation and tumour immunology. METHODS:In this review, we describe the use of specific radiopharmaceuticals for infectious and inflammatory diseases with the aim of fast and accurate diagnosis and treatment follow-up. Furthermore, we focus on specific oncological indications with an emphasis on tumour immunology and visualizing the tumour environment. RESULTS:Molecular nuclear medicine imaging techniques get a foothold in the diagnosis of a variety of infectious and inflammatory diseases, such as bacterial and fungal infections, rheumatoid arthritis, and large vessel vasculitis, but also for treatment response in cancer immunotherapy. CONCLUSION:Several specific radiopharmaceuticals can be used to improve diagnosis and staging, but also for therapy decision-making and follow-up in infectious, inflammatory and oncological diseases where immune cells are involved. The identification of these cell subpopulations by nuclear medicine techniques would provide personalized medicine for these patients, avoiding side effects and improving therapeutic approaches.

SUBMITTER: Signore A

PROVIDER: S-EPMC6571748 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Immuno-Imaging to Predict Treatment Response in Infection, Inflammation and Oncology.

Signore Alberto A Lauri Chiara C Auletta Sveva S Anzola Kelly K Galli Filippo F Casali Massimiliano M Versari Annibale A Glaudemans Andor W J M AWJM

Journal of clinical medicine 20190514 5

<h4>Background</h4>Molecular nuclear medicine plays a pivotal role for diagnosis in a preclinical phase, in genetically susceptible patients, for radio-guided surgery, for disease relapse evaluation, and for therapy decision-making and follow-up. This is possible thanks to the development of new radiopharmaceuticals to target specific biomarkers of infection, inflammation and tumour immunology.<h4>Methods</h4>In this review, we describe the use of specific radiopharmaceuticals for infectious and ...[more]

PMID: 31091813

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Project description:ImportanceThe association between treatment with first-line immuno-oncology (IO) combination therapies and physician-assessed objective imaging response among patients with metastatic renal cell carcinoma (mRCC) remains uncharacterized.ObjectiveTo compare the likelihood of objective imaging response (ie, complete or partial response) to first-line IO combination ipilimumab-nivolumab (IOIO) therapy vs approved IO with vascular endothelial growth factor inhibitor (IOVE) combination therapies among patients with mRCC.Design, setting, and participantsThis multicenter international cohort study was nested in routine clinical practice. A data set from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) was used to identify consecutive patients with mRCC who received treatment with IO combination therapies between May 30, 2013, and September 9, 2021. A total of 899 patients with a histologically confirmed diagnosis of mRCC who received treatment with a first-line IOVE or IOIO regimen and had evaluable responses were included.ExposuresBest overall response to first-line IO combination therapy based on Response Evaluation Criteria in Solid Tumors, version 1.1.Main outcomes and measuresThe primary outcome was the difference in treating physician-assessed objective imaging response based on the type of first-line IO combination therapy received. Secondary outcomes included the identification of baseline characteristics positively associated with objective imaging response and the association of objective imaging response with overall survival.ResultsAmong 1085 patients with mRCC who received first-line IO combination therapies, 899 patients (median age, 62.8 years [IQR, 55.9-69.2 years]; 666 male [74.2%]) had evaluable responses. A total of 794 patients had information available on IMDC risk classification; of those, 127 patients (16.0%) had favorable risk, 442 (55.7%) had intermediate risk, and 225 (28.3%) had poor risk. With regard to best overall response among all participants, 37 patients (4.1%) had complete response, 344 (38.3%) had partial response, 315 (35.0%) had stable disease, and 203 (22.6%) had progressive disease. Corresponding median overall survival was not estimable (95% CI, 53.3 months to not estimable) among patients with complete response, 55.9 months (95% CI, 44.1 months to not estimable) among patients with partial response, 48.1 months (95% CI, 33.4 months to not estimable) among patients with stable disease, and 13.0 months (95% CI, 8.4-18.1 months) among patients with progressive disease (log rank P < .001). Treatment with IOVE therapy was found to be independently associated with an increased likelihood of obtaining response (OR, 1.89; 95% CI, 1.26-2.81; P = .002) compared with IOIO therapy. The presence of lung metastases (odds ratio [OR], 1.49; 95% CI, 1.01-2.20), receipt of cytoreductive nephrectomy (OR, 1.59; 95% CI, 1.04-2.43), and favorable IMDC risk (OR, 1.93; 95% CI, 1.10-3.39) were independently associated with an increased likelihood of response.Conclusions and relevanceIn this study, treatment with IOVE therapy was associated with significantly increased odds of objective imaging response compared with IOIO therapy. The presence of lung metastases, receipt of cytoreductive nephrectomy, and favorable IMDC risk were associated with increased odds of experiencing objective imaging response. These findings may help inform treatment selection, especially in clinical contexts associated with high-volume multisite metastatic disease, in which obtaining objective imaging response is important.

Project description:Immune checkpoint inhibitors (ICI) revolutionized the field of immuno-oncology and opened new avenues towards the development of novel assets to achieve durable immune control of cancer. Yet, the presence of tumor immune evasion mechanisms represents a challenge for the development of efficient treatment options. Therefore, combination therapies are taking the center of the stage in immuno-oncology. Such combination therapies should boost anti-tumor immune responses and/or target tumor immune escape mechanisms, especially those created by major players in the tumor microenvironment (TME) such as tumor-associated macrophages (TAM). Natural killer (NK) cells were recently positioned at the forefront of many immunotherapy strategies, and several new approaches are being designed to fully exploit NK cell antitumor potential. One of the most relevant NK cell-activating receptors is NKG2D, a receptor that recognizes 8 different NKG2D ligands (NKG2DL), including MICA and MICB. MICA and MICB are poorly expressed on normal cells but become upregulated on the surface of damaged, transformed or infected cells as a result of post-transcriptional or post-translational mechanisms and intracellular pathways. Their engagement of NKG2D triggers NK cell effector functions. Also, MICA/B are polymorphic and such polymorphism affects functional responses through regulation of their cell-surface expression, intracellular trafficking, shedding of soluble immunosuppressive isoforms, or the affinity of NKG2D interaction. Although immunotherapeutic approaches that target the NKG2D-NKG2DL axis are under investigation, several tumor immune escape mechanisms account for reduced cell surface expression of NKG2DL and contribute to tumor immune escape. Also, NKG2DL polymorphism determines functional NKG2D-dependent responses, thus representing an additional challenge for leveraging NKG2DL in immuno-oncology. In this review, we discuss strategies to boost MICA/B expression and/or inhibit their shedding and propose that combination strategies that target MICA/B with antibodies and strategies aimed at promoting their upregulation on tumor cells or at reprograming TAM into pro-inflammatory macrophages and remodeling of the TME, emerge as frontrunners in immuno-oncology because they may unleash the antitumor effector functions of NK cells and cytotoxic CD8 T cells (CTL). Pursuing several of these pipelines might lead to innovative modalities of immunotherapy for the treatment of a wide range of cancer patients.

Dataset Information

Immuno-Imaging to Predict Treatment Response in Infection, Inflammation and Oncology.

Publications

Immuno-Imaging to Predict Treatment Response in Infection, Inflammation and Oncology.

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