Genomics- and Transcriptomics-Based Patient Selection for Cancer Treatment With Immune Checkpoint Inhibitors

Dijkstra, Krijn K.; Voabil, Paula; Schumacher, Ton N.; Voest, Emile E.

doi:10.1001/jamaoncol.2016.2214

Cited by 74 publications

(53 citation statements)

References 54 publications

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“…It is currently a matter of debate which biomarkers may best predict response to checkpoint inhibitors. Mutational burden, composition and activity of a preexisting immune infiltrate and mechanisms of tumor escape from immune surveillance are considered important components associated with the probability of response (Dijkstra et al 2016).…”

Section: Immunotherapy In Neuroendocrine Tumorsmentioning

confidence: 99%

WOMEN IN CANCER THEMATIC REVIEW: Systemic therapies in neuroendocrine tumors and novel approaches toward personalized medicine

Pavel¹,

Sers²

2016

Endocrine-Related Cancer

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Neuroendocrine tumors (NETs) are a group of heterogenous neoplasms. Evidencebased treatment options for antiproliferative therapy include somatostatin analogues, the mTOR inhibitor everolimus, the multiple tyrosine kinase inhibitor sunitinib and peptide receptor radionuclide therapy with 177-Lu-octreotate. In the absence of definite predictive markers, therapeutic decision making follows clinical and pathological criteria. As objective response rates with targeted drugs are rather low, and response duration is limited in most patients, numerous combination therapies targeting multiple pathways have been explored in the field. Upfront combination of drugs, however, is associated with increasing toxicity and has shown little benefit. Major advancements in the molecular understanding of NET based on genomic, epigenomic and transcriptomic analysis have been achieved with prognostic and therapeutic impact. New insight into molecular alterations has paved the way to biomarker-driven clinical trials and may facilitate treatment stratification toward personalized medicine in the near future. However, an improved understanding of the complexity of pathway interactions is required for successful treatment. A systems biology approach is one of the tools that may help to achieve this endeavor.

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Section: Immunotherapy In Neuroendocrine Tumorsmentioning

confidence: 99%

WOMEN IN CANCER THEMATIC REVIEW: Systemic therapies in neuroendocrine tumors and novel approaches toward personalized medicine

Pavel¹,

Sers²

2016

Endocrine-Related Cancer

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“…Despite these encouraging results, a large fraction of patients does not respond to current immunotherapies. Treatment failure may be explained at many different levels that include a low number of immunogenic antigens, defective antigen presentation, and/or the expression of alternative immune checkpoint molecules (Blank et al, 2016; Dijkstra et al, 2016; Pitt et al, 2017; Sharma et al, 2017). Given the large variety in mechanisms of immune evasion by cancers, it is presently challenging to predict whether an individual patient will be sensitive to immunotherapy, what mechanism is likely to underlie resistance and what alternative treatment could potentially overcome such resistance.…”

Section: Introductionmentioning

confidence: 99%

Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids

Dijkstra

Cattaneo

Weeber

et al. 2018

Cell

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775

711

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Cancer immunotherapies have shown substantial clinical activity for a subset of patients with epithelial cancers. Still, technological platforms to study cancer T-cell interactions for individual patients and understand determinants of responsiveness are presently lacking. Here, we establish and validate a platform to induce and analyze tumor-specific T cell responses to epithelial cancers in a personalized manner. We demonstrate that co-cultures of autologous tumor organoids and peripheral blood lymphocytes can be used to enrich tumor-reactive T cells from peripheral blood of patients with mismatch repair-deficient colorectal cancer and non-small-cell lung cancer. Furthermore, we demonstrate that these T cells can be used to assess the efficiency of killing of matched tumor organoids. This platform provides an unbiased strategy for the isolation of tumor-reactive T cells and provides a means by which to assess the sensitivity of tumor cells to T cell-mediated attack at the level of the individual patient.

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“…Programmed death ligand 1 (PD‐L1) is a transmembrane protein expressed on immune cells (IC) and tumour cells (TC), whereas programmed cell death (PD)‐1 is expressed on IC and its expression can be induced following T cell activation. Upon binding to the receptor PD‐1 in IC, the overexpressed PD‐L1 in TC leads to functional inactivation of T cells and down‐regulation of T cell antitumoral activity, resulting in immune evasion . In recent years, PD‐L1 and PD‐1 have emerged as a key check‐point that can be manipulated with inhibitory monoclonal antibodies in various cancer types.…”

Section: Introductionmentioning

confidence: 99%

“…Upon binding to the receptor PD-1 in IC, the overexpressed PD-L1 in TC leads to functional inactivation of T cells and down-regulation of T cell antitumoral activity, resulting in immune evasion. [1][2][3][4][5] In recent years, PD-L1 and PD-1 have emerged as a key check-point that can be manipulated with inhibitory monoclonal antibodies in various cancer types. Multiple prospective randomised clinical trials have shown promising results of PD-1/PD-L1 immune check-point inhibitors in a variety of cancer types, including a subset of patients with urothelial carcinoma (UC), [5][6][7][8] breast carcinoma (BC) 9,10 and head and neck squamous cell carcinoma (HSCC), [11][12][13][14] leading to the Food and Drug Administration (FDA) approval of several anti-PD-1/ PD-L1 agents.…”

Section: Introductionmentioning

confidence: 99%

Inter‐ and intraobserver agreement of programmed death ligand 1 scoring in head and neck squamous cell carcinoma, urothelial carcinoma and breast carcinoma

et al. 2019

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Aims Programmed death‐ligand 1 (PD‐L1) expression by tumour cells (TC) is a mechanism for tumour immune escape through down‐regulation of antitumour T cell responses and is a target for immunotherapy. PD‐L1 status as a predictor of treatment response has led to the development of multiple biomarkers with different reference cut‐offs. We assessed pathologist consistency in evaluating PD‐L1 immunopositivity by examining the inter‐ and intraobserver agreement using various antibody clones and different cancer types. Methods and results PD‐L1 expression in TC and immune cells (IC) was manually scored in 27 head and neck squamous cell carcinoma (HSCC), 30 urothelial carcinoma (UC) and breast carcinoma (BC) using three commercial clones (SP263, SP142, 22C3) and one platform‐independent test (E1L3N). For interobserver agreement, PD‐L1 status was evaluated blindly by three pathologists. For intraobserver agreement, PD‐L1 expression was re‐evaluated following a wash‐out period. Intraclass correlation coefficient (ICC), overall percentage agreement (OPA) and κ‐values were calculated. Using clinical algorithms, the percentage of PD‐L1‐positive cases in HSCC, BC and UC were 15–81%, 47–67% and 7–43%, respectively. The percentage of PD‐L1 positive cases relied heavily on the algorithm/cut‐off values used. Almost perfect interobserver agreement was achieved using SP263 and E1L3N in HSCC, 22C3, SP142 and E1L3N in BC and 22C3 in UC. The SP142 clone in UC and HSCC showed moderate agreement and was associated with lower ICC and decreased intraobserver concordance. Conclusions Excellent inter‐ and intraobserver agreement can be achieved using SP263, 22C3 and E1L3N, whereas PD‐L1 scoring using SP142 clone is associated with a higher level of subjectivity.

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Genomics- and Transcriptomics-Based Patient Selection for Cancer Treatment With Immune Checkpoint Inhibitors

Cited by 74 publications

References 54 publications

WOMEN IN CANCER THEMATIC REVIEW: Systemic therapies in neuroendocrine tumors and novel approaches toward personalized medicine

WOMEN IN CANCER THEMATIC REVIEW: Systemic therapies in neuroendocrine tumors and novel approaches toward personalized medicine

Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids

Inter‐ and intraobserver agreement of programmed death ligand 1 scoring in head and neck squamous cell carcinoma, urothelial carcinoma and breast carcinoma

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