Whole-body CD8+ T cell visualization before and during cancer immunotherapy: a phase 1/2 trial

Ruijter, Laura Kist de; Donk, Pim P. van de; Hooiveld-Noeken, Jahlisa S.; Giesen, Danique; Elias, Sjoerd G.; Hooge, Marjolijn N. Lub-de; Oosting, Sjoukje F.; Jalving, Mathilde; Timens, Wim; Brouwers, Adrienne H.; Kwee, Thomas C.; Gietema, Jourik A.; Fehrmann, Rudolf S.N.; Fine, Bernard M.; Bohórquez, Sandra M Sanabria; Yadav, Mahesh; Koeppen, Hartmut; Jing, Jing; Guelman, Sebastián; Lin, Mark T; Mamounas, Michael; Eastham, Jeffrey; Kimes, Patrick K.; Williams, Simon P.; Ungewickell, Alexander; Groot, Derk Jan A. de; Vries, Elisabeth G.E. de

doi:10.1038/s41591-022-02084-8

Cited by 63 publications

(44 citation statements)

References 52 publications

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“…However, we are also keenly aware of the inherent caveat of the approach of interrogating an environment of high plasticity such as the TME in archival tissues to predict therapy outcome. There is ample clinical and experimental evidence that tumor IP can change during immunotherapy [47] [48] [49] [50]; in vivo imaging approaches could circumvent the need for on-treatment biopsies for immune profiling [51].…”

Section: Discussionmentioning

confidence: 99%

Automated tumor immunophenotyping predicts clinical benefit from anti-PD-L1 immunotherapy

Li¹,

Eastham²,

Zou³

et al. 2023

Preprint

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Background. Cancer immunotherapy has transformed the clinical approach to patients with malignancies as profound benefits can be seen in a subset of patients. To identify this subset, biomarker analyses increasingly focus on phenotypic and functional evaluation of the tumor microenvironment (TME) to determine if density, spatial distribution, and cellular composition of immune cell infiltrates can provide prognostic and/or predictive information. Attempts have been made to develop standardized methods to evaluate immune infiltrates in the routine assessment of certain tumor types; however, broad adoption of this approach in clinical decision-making is still missing. Methods. We developed approaches to categorize solid tumors into "Desert", "Excluded" and "Inflamed" types according to the spatial distribution of CD8+ immune effector cells to determine the prognostic and/or predictive implications of such labels. To overcome the limitations of this subjective approach we incrementally developed four automated analysis pipelines of increasing granularity and complexity for density and pattern assessment of immune effector cells. Results. We show that categorization based on "manual" observation is predictive for clinical benefit from anti-programmed cell death ligand-1 (PD-L1) therapy in two large cohorts of patients with non-small cell lung cancer (NSCLC) or triple-negative breast cancer (TNBC). For the automated analysis we demonstrate that a combined approach outperforms individual pipelines and successfully relates spatial features to pathologist-based read-outs and patient response to therapy. Conclusions. Our findings suggest tumor immunophenotype (IP) generated by automated analysis pipelines should be evaluated further as potential predictive biomarkers for cancer immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Automated tumor immunophenotyping predicts clinical benefit from anti-PD-L1 immunotherapy

Li¹,

Eastham²,

Zou³

et al. 2023

Preprint

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“…Patients (n = 15 (5 men, 10 women; age 33-79, mean ± SD 58 ± 13 years; weight 52-109, mean ± SD 73 ± 15 kg) with cancer with visible [ 89 Zr]mAb PET tracer uptake at day 4 p.i. in at least one tumour lesion were enrolled in this prospective study between June 2018 and February 2020 in case of a referral for an 89 Zr immunoPET acquisition to solve a clinical dilemma [14,15] or for research purposes (ClinicalTrials.gov identifiers NCT02453984 [16] and NCT04029181 [17]). All patients were scanned on the Vision PET/CT system.…”

Section: Patient Populationmentioning

confidence: 99%

Optimisation of scan duration and image quality in oncological 89Zr immunoPET imaging using the Biograph Vision PET/CT

Sluis

Boellaard

Dierckx

et al. 2023

Eur J Nucl Med Mol Imaging

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Purpose Monoclonal antibody (mAb)-based PET (immunoPET) imaging can characterise tumour lesions non-invasively. It may be a valuable tool to determine which patients may benefit from treatment with a specific monoclonal antibody (mAb) and evaluate treatment response. For 89Zr immunoPET imaging, higher sensitivity of state-of-the art PET/CT systems equipped with silicon photomultiplier (SiPM)-based detector elements may be beneficial as the low positron abundance of 89Zr causes a low signal-to-noise level. Moreover, the long physical half-life limits the amount of activity that can be administered to the patients leading to poor image quality even when using long scan durations. Here, we investigated the difference in semiquantitative performance between the PMT-based Biograph mCT, our clinical reference system, and the SiPM-based Biograph Vision PET/CT in 89Zr immunoPET imaging. Furthermore, the effects of scan duration reduction using the Vision on semiquantitative imaging parameters and its influence on image quality assessment were evaluated. Methods Data were acquired on day 4 post 37 MBq 89Zr-labelled mAb injection. Five patients underwent a double scan protocol on both systems. Ten patients were scanned only on the Vision. For PET image reconstruction, three protocols were used, i.e. one camera-dependent protocol and European Association of Nuclear Medicine Research Limited (EARL) standards 1 and 2 compliant protocols. Vision data were acquired in listmode and were reprocessed to obtain images at shorter scan durations. Semiquantitative PET image parameters were derived from tumour lesions and healthy tissues to assess differences between systems and scan durations. Differently reconstructed images obtained using the Vision were visually scored regarding image quality by two nuclear medicine physicians. Results When images were reconstructed using 100% acquisition time on both systems following EARL standard 1 compliant reconstruction protocols, results regarding semiquantification were comparable. For Vision data, reconstructed images that conform to EARL1 standards still resulted in comparable semiquantification at shorter scan durations (75% and 50%) regarding 100% acquisition time. Conclusion Scan duration of 89Zr immunoPET imaging using the Vision can be decreased up to 50% compared with using the mCT while maintaining image quality using the EARL1 compliant reconstruction protocol.

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“…The positive predictive value of CD8+ cytotoxic T cells was found across 17 solid cancer types, including colorectal, breast, melanoma, lung, head and neck and others ( 12 ). Because of the vital role that the CD8+ T cells play in therapy response and clinical outcome, imaging agents that are being developed for non-invasive immunomonitoring aim to characterize different aspects of the CD8+ subset – their abundance ( 13 , 14 ), activation ( 15 , 16 ) or effector function ( 17 ). The degree of specificity for CD8+ T cells among the metabolic tracers that are the focus of this mini review, varies depending on what metabolic pathway they target ( 18 ).…”

Section: Imaging Targetsmentioning

confidence: 99%

The other immuno-PET: Metabolic tracers in evaluation of immune responses to immune checkpoint inhibitor therapy for solid tumors

Levi

Song

2023

Front. Immunol.

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Unique patterns of response to immune checkpoint inhibitor therapy, discernable in the earliest clinical trials, demanded a reconsideration of the standard methods of radiological treatment assessment. Immunomonitoring, that characterizes immune responses, offers several significant advantages over the tumor-centric approach currently used in the clinical practice: 1) better understanding of the drugs’ mechanism of action and treatment resistance, 2) earlier assessment of response to therapy, 3) patient/therapy selection, 4) evaluation of toxicity and 5) more accurate end-point in clinical trials. PET imaging in combination with the right agent offers non-invasive tracking of immune processes on a whole-body level and thus represents a method uniquely well-suited for immunomonitoring. Small molecule metabolic tracers, largely neglected in the immuno-PET discourse, offer a way to monitor immune responses by assessing cellular metabolism known to be intricately linked with immune cell function. In this review, we highlight the use of small molecule metabolic tracers in imaging immune responses, provide a view of their value in the clinic and discuss the importance of image analysis in the context of tracking a moving target.

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Whole-body CD8+ T cell visualization before and during cancer immunotherapy: a phase 1/2 trial

Cited by 63 publications

References 52 publications

Automated tumor immunophenotyping predicts clinical benefit from anti-PD-L1 immunotherapy

Automated tumor immunophenotyping predicts clinical benefit from anti-PD-L1 immunotherapy

Optimisation of scan duration and image quality in oncological 89Zr immunoPET imaging using the Biograph Vision PET/CT

The other immuno-PET: Metabolic tracers in evaluation of immune responses to immune checkpoint inhibitor therapy for solid tumors

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