Pia Kvistborg

Pia Kvistborg
Netherlands Cancer Institute · Division of Immunology

About

96
Publications
28,258
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
11,529
Citations
Citations since 2017
47 Research Items
9603 Citations
201720182019202020212022202305001,0001,500
201720182019202020212022202305001,0001,500
201720182019202020212022202305001,0001,500
201720182019202020212022202305001,0001,500

Publications

Publications (96)
Article
9552 Background: Continuous combination of MAPK pathway inhibition (MAPKi) and anti-PD-(L)1 showed high response rates, but also high frequency of treatment-related adverse events (TRAE) in BRAFV600-mutated melanoma patients (pts). Short‐time MAPKi already induces T cell infiltration in pts and was synergistic with anti-PD‐1 in a pre-clinical model...
Article
Full-text available
Since the start of the COVID-19 pandemic, mutations have led to the emergence of new SARS-CoV-2 variants, and some of these have become prominent or dominant variants of concern. This natural course of development can have an impact on how protective the previously naturally or vaccine induced immunity is. Therefore, it is crucial to understand whe...
Preprint
Full-text available
Since the start of the COVID-19 pandemic, mutations have led to the emergence of new SARS-CoV-2 variants, and some of these have become prominent or dominant variants of concern. This natural course of development can have an impact on how protective the previously naturally or vaccine induced immunity is. Therefore, it is crucial to understand whe...
Article
Full-text available
The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences b...
Article
Background Patients with cancer have an increased risk of complications from SARS-CoV-2 infection. Vaccination to prevent COVID-19 is recommended, but data on the immunogenicity and safety of COVID-19 vaccines for patients with solid tumours receiving systemic cancer treatment are scarce. Therefore, we aimed to assess the impact of immunotherapy, c...
Article
Full-text available
Significance Despite the success of checkpoint-targeting therapies, many melanoma patients do not respond or acquire resistance after initial responsiveness. A better understanding about the mechanism by which these therapies enhance immune-mediated tumor control is key to providing the rationale for better treatment strategies. In this study, we s...
Conference Paper
p>Neoantigens, which are antigens specific to cancer cells, can be harnessed to develop precision immunotherapies, such as personalized cancer vaccines, and prognostic biomarkers for checkpoint blockade inhibition. Next generation sequencing technologies have enabled comprehensive profiling of putative neoantigens by interrogating the tumor exome a...
Article
Full-text available
The human leukocyte antigen (HLA)-bound-viral antigens serve as an immunological signature that can be selectively recognized by T cells. As viruses evolve by acquiring mutations, it is essential to identify a range of viral presented antigens. Utilizing HLA-peptidomics we were able to identify SARS-CoV-2-derived peptides presented by highly preval...
Article
Full-text available
The COVID-19 pandemic caused by SARS-CoV-2 is a continuous challenge worldwide, and there is an urgent need to map the landscape of immunogenic and immunodominant epitopes recognized by CD8+ T cells. Here, we analyze samples from 31 patients with COVID-19 for CD8+ T cell recognition of 500 peptide-HLA class I complexes, restricted by 10 common HLA...
Article
Full-text available
Approximately 15% of advanced head and neck squamous cell carcinomas (HNSCC) respond to anti-PD-(L)1 monotherapies. Tumor PD-L1 expression and human papillomavirus (HPV) status have been proposed as biomarkers to identify patients likely to benefit from these treatments. We aimed to understand the potential immune effects of HPV in HNSCC and to cha...
Article
Full-text available
A variety of species of bacteria are known to colonize human tumours1–11, proliferate within them and modulate immune function, which ultimately affects the survival of patients with cancer and their responses to treatment12–14. However, it is not known whether antigens derived from intracellular bacteria are presented by the human leukocyte antige...
Preprint
Full-text available
Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have revolutionized the treatment of melanoma patients. Based on early studies addressing the mechanism of action, it was assumed that PD-1 blockade mostly influences T cell responses at the tumor site. However, rec...
Article
Full-text available
Preoperative immunotherapy with anti-PD1 plus anti-CTLA4 antibodies has shown remarkable pathological responses in melanoma¹ and colorectal cancer². In NABUCCO (ClinicalTrials.gov: NCT03387761), a single-arm feasibility trial, 24 patients with stage III urothelial cancer (UC) received two doses of ipilimumab and two doses of nivolumab, followed by...
Article
Full-text available
Background The profound disparity in response to immune checkpoint blockade (ICB) by cutaneous melanoma (CM) and uveal melanoma (UM) patients is not well understood. Therefore, we characterized metastases of CM and UM from the same metastatic site (liver), in order to dissect the potential underlying mechanism in differential response on ICB. Meth...
Article
Full-text available
Background Global efforts are ongoing to develop vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease (COVID-19). While there is accumulating information on antibody responses against SARS-CoV-2, less is known about CD8 T-cell recognized SARS-CoV-2 epitopes and the functional state of SARS-CoV-2-...
Article
Many approaches to identify therapeutically relevant neoantigens couple tumor sequencing with bioinformatic algorithms and inferred rules of tumor epitope immunogenicity. However, there are no reference data to compare these approaches, and the parameters governing tumor epitope immunogenicity remain unclear. Here, we assembled a global consortium...
Conference Paper
While there is accumulating evidence on the antibody response against SARS-CoV-2, we are only beginning to acquire knowledge regarding the SARS-CoV-2 specific CD8 T-cell response. Therefore, it is an urgent matter to gain a deeper insight into the virus specific CD8 T-cell response to both assist vaccine design and provide tools to evaluate the vac...
Conference Paper
Neoantigen-based therapies hold the promise of being safe, personalized anti-cancer therapies for a broad range of cancers. A crucial step for the development of effective neoantigen therapies is the identification of putative tumor specific neoantigens typically achieved through in silico analyses. In silico-based approaches have the benefit of be...
Article
Full-text available
Treatment of metastatic melanoma with autologous tumor infiltrating lymphocytes (TILs) is currently applied in several centers. Robust and remarkably consistent overall response rates, of around 50% of treated patients, have been observed across hospitals, including a substantial fraction of durable, complete responses. Purpose Execute a phase I/I...
Preprint
Full-text available
A large global effort is currently ongoing to develop vaccines against SARS-CoV-2, the causative agent of COVID-19. While there is accumulating evidence on the antibody response against SARS-CoV-2, little is known about the SARS-CoV-2 antigens that are targeted by CD8 T cells. To address this issue, we have analyzed samples from 20 COVID-19 patient...
Preprint
Full-text available
Global efforts are ongoing to develop vaccines against SARS-CoV-2 causing COVID-19. While there is accumulating information on antibody responses against SARS-CoV-2, less is known about CD8 T-cell recognized SARS-CoV-2 epitopes and the functional state of SARS- CoV-2-specific CD8 T cells. To address these issues, we analyzed samples from 18 COVID-...
Article
10021 Background: Continuous combination of MAPK inhibition (MAPKi) and anti-PD-(L)1 has been investigated by several trials to improve outcome of BRAFV600 mutated melanoma patients. A major obstacle for continuous combination is the high frequency (~60%) of grade 3-4 treatment-related adverse events (TRAE) for which many patients need to discontin...
Article
5020 Background: Encouraging pathological complete response (pCR) rates were observed in trials testing neoadjuvant pembrolizumab or atezolizumab in urothelial cancer (UC). In cT3-4N0 tumors, pCR to atezolizumab was only 17% and restricted to tumors showing characteristics of preexisting T cell immunity. In NABUCCO, we aimed to increase response to...
Poster
Full-text available
ESMO 2019; M.S. van der Heijden, N. van Dijk, L. Smit, K. Hendricksen, J.M. de Feijter, E. Bekers, E. Hooijberg, C.C.N. van Rooijen, A. Broeks, Y. Lubeck, K. Sikorska, T. Schumacher, P. Kvistborg, T. Boellaard, C.U. Blank, B.W. van Rhijn Study with combination immunotherapy prior to surgery for bladder cancer shows positive results A study of 24...
Article
Background Stage III (cT3-4aN0M0 or ≥cT1N+M0) urothelial cancer (UC) patients (pts) have a poor prognosis. Despite high response rates, pre-operative chemo shows limited survival benefit. Immunotherapy targeting PD-1/PD-L1 is active in metastatic UC; the combination of ipilimumab (ipi) and nivolumab (nivo) appears to increase response rates. Encour...
Article
Malignant transformation of cells depends on accumulation of DNA damage. Over the past years we have learned that the T cell–based immune system frequently responds to the neoantigens that arise as a consequence of this DNA damage. Furthermore, recognition of neoantigens appears an important driver of the clinical activity of both T cell checkpoint...
Article
Effector T cell responses directed toward cancer neoantigens mediate tumor regression following checkpoint blockade or adoptive T cell immunotherapy, but are generally "private", thus requiring considerable effort for their identification. In this issue of the JCI, Malekzadeh et al. show that a fraction of patients with epithelial cancers mount ant...
Conference Paper
p>Over the past years we have learned that the T-cell-based immune system frequently responds to the neoantigens that arise as a consequence of the accumulated DNA damage causing the malignant transformation. Furthermore, recognition of neoantigens appears an important driver of the clinical activity of both T-cell checkpoint blockade and adoptive...
Article
Full-text available
The treatment of metastatic melanoma patients with autologous tumor-infiltrating lymphocytes (TIL) shows robust, reproducible, clinical responses in clinical trials executed in several specialized centers over the world. Even in the era of targeted therapy and immune checkpoint inhibition, TIL therapy can be an additional and clinically relevant tr...
Article
Full-text available
Many metastatic melanoma patients experience durable responses to anti-PD1 and/or anti-CTLA4, however, a significant proportion (over 50%) do not benefit from the therapies. In this study, we sought to assess pretreatment liquid biopsies for biomarkers that may correlate with response to checkpoint blockade. We measured the combinatorial diversity...
Article
Full-text available
Adjuvant ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) both improve relapse-free survival of stage III melanoma patients1,2. In stage IV disease, the combination of ipilimumab + nivolumab is superior to ipilimumab alone and also appears to be more effective than nivolumab monotherapy³. Preclinical work suggests that neoadjuvant application of...
Article
Approximately 20% of advanced SCCHNs respond to anti-PD-(L)1. We aimed to inform rational combination therapy development, which might have greater efficacy, by understanding the potential immune effects of the oncogenic human papillomavirus (HPV) in SCCHN, and by characterizing potentially targetable immune checkpoints in the tumor microenvironmen...
Article
The capacity of antigen presentation influences responses to checkpoint immunotherapy
Chapter
The development of peptide loaded major histocompatibility complexes (MHC) conjugated to fluorochromes by Davis and colleagues 20 years ago provided a highly useful tool to identify and characterize antigen-specific T cells. In this chapter we describe a multiplexing strategy that allows detection of high numbers of T cell responses in parallel.
Article
Full-text available
Background: Usual type vulvar intraepithelial neoplasia (uVIN) is caused by HPV, predominantly type 16. Several forms of HPV immunotherapy have been studied, however, clinical results could be improved. A novel intradermal administration route, termed DNA tattooing, is superior in animal models, and was tested for the first time in humans with a H...
Article
Cancer immunotherapy can result in durable tumor regressions in some patients. However, patients who initially respond often experience tumor progression. Here we report mechanistic evidence of tumoral immune escape in an exemplary clinical case: a patient with metastatic melanoma who developed disease recurrence following an initial, unequivocal r...
Article
9586 Background: The combination of IPI+NIVO induces high response rates and improved overall survival in late stage melanoma. T cell checkpoint inhibition is of greatest value at the moment of TCR triggering and therefore dependent on the amount of antigen present, indicating that adjuvant immunotherapy may work most efficiently, when initiated pr...
Poster
Background: Anti-PD-1 and/or anti-CTLA-4 antibodies show durable responses in metastatic melanoma. Measuring the diversity of T-lymphocytes in pre-treatment liquid biopsies may help stratify patients for immunotherapy. Methods: In this retrospective blinded study, we used a multi-N-plex polymerase chain reaction assay to measure T-cell receptors (T...
Article
Purpose Autologous monocyte-derived dendritic cells (DCs) electroporated with synthetic mRNA (TriMixDC-MEL) are immunogenic and have antitumor activity as a monotherapy in patients with pretreated advanced melanoma. Ipilimumab, an immunoglobulin G1 monoclonal antibody directed against the cytotoxic T-lymphocyte-associated protein 4 receptor that co...
Article
Full-text available
Cancer vaccine development has been vigorously pursued for 40 years. Immunity to tumor antigens can be elicited bymost vaccines tested, but their clinical efficacy remainsmodest.We argue that a concerted international effort is necessary to understand the human antitumor immune response and achieve clinically effective cancer vaccines.
Article
Full-text available
The culmination of over a century's work to understand the role of the immune system in tumor control has led to the recent advances in cancer immunotherapies that have resulted in durable clinical responses in patients with a variety of malignancies. Cancer immunotherapies are rapidly changing traditional treatment paradigms and expanding the ther...
Article
Tumor infiltrating lymphocyte (TIL) therapy has shown objective clinical response rates of 50% in stage IV melanoma patients in a number of clinical trials. Nevertheless, the majority of patients progress either directly upon therapy or after an initial period of tumor control. Recent data have shown that most TIL products that are used for therapy...
Article
Infusion of tumor-infiltrating T-lymphocytes was developed as treatment for metastatic melanoma by Dr. S. Rosenberg (Surgery Branch, NIH, Bethesda, MD, USA) in the late 90's of the past century. This therapy was based on the finding that melanomas oftentimes have infiltrates of CD8 T cells that show recognition of melanoma cells. Many tumor antigen...
Article
Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA The mutational load in melanoma is high relative to that in most other human malignancies, resulting in the possible expression of large numbers of patient-specific mutated antigens. This may, in part, explain the immunogenicity of this disease and the high rate of re...
Article
Full-text available
Immune checkpoint-blocking therapies have yielded positive clinical data in a series of human malignancies. Recent work from Le and colleagues strongly supports the use of these therapies for mismatch repair-deficient tumors, independent of underlying tumor type. These data suggest the importance of sensing the consequences of DNA damage in cancer...
Article
Present address: Immuno-Oncology & Combinations DPU, Oncology RDBendall et al., 2011), allowing an oppor-tunity to better understand the immuno-logical mechanisms underlying disease.Complex flow cytometry (FCM) data arenow surpassing our ability to fully analyzeand interpret all information via currentstandard approaches, such as 2D dotplots and Boo...
Article
Full-text available
Immune checkpoint inhibitors, which unleash a patient's own T cells to kill tumors, are revolutionizing cancer treatment. To unravel the genomic determinants of response to this therapy, we used whole-exome sequencing of non-small cell lung cancers treated with pembrolizumab, an antibody targeting programmed cell death-1 (PD-1). In two independent...
Article
Full-text available
Anti-CTLA-4 treatment improves the survival of patients with advanced-stage melanoma. However, although the anti-CTLA-4 antibody ipilimumab is now an approved treatment for patients with metastatic disease, it remains unknown by which mechanism it boosts tumor-specific T cell activity. In particular, it is unclear whether treatment amplifies previo...
Article
Advances in genetic engineering have made it possible to generate human T cell products that carry desired functionalities, such as the ability to recognize cancer cells. The currently used strategies for the generation of gene-modified T cell products lead to highly differentiated cells within the infusion product, and on the basis of data obtaine...
Chapter
It is now beyond doubt that different human tumor types can be recognized by the immune system and that cytotoxic T cells are a key player in this process. For long, efforts to understand and influence such tumor-specific T-cell reactivity have focused on the tumor-associated “self-antigens” that are also expressed in other tissues. However, many o...
Article
Full-text available
Peptide-MHC (pMHC) multimers have become one of the most widely used tools to measure Ag-specific T cell responses in humans. With the aim of understanding the requirements for pMHC-based personalized immunomonitoring, in which individuals expressing subtypes of the commonly studied HLA alleles are encountered, we assessed how the ability to detect...
Article
Full-text available
Tumor infiltrating lymphocyte (TIL) therapy has shown objective clinical response rates of 50% in stage IV melanoma patients in a number of clinical trials. Nevertheless, the majority of patients progress either directly upon therapy or after an initial period of tumor control. Recent data have shown that most TIL products that are used for therapy...
Article
Full-text available
The transfer of T cell receptor (TCR) genes into patient T cells is a promising approach for the treatment of both viral infections and cancer. Although efficient methods exist to identify antibodies for the treatment of these diseases, comparable strategies to identify TCRs have been lacking. We have developed a high-throughput DNA-based strategy...
Article
Full-text available
The evidence for T-cell–mediated regression of human cancers such as non–small-cell lung carcinoma, renal cell carcinoma, and—in particular—melanoma after immunotherapy is strong. Anti-CTLA4 (ipilimumab) treatment has been approved for treatment of meta-static melanoma,1 and antibody-mediated blockade of PD-1, a second inhibitory receptor on T cell...
Article
9078 Background: There is strong evidence that melanoma-reactive T cells induced by immunotherapeutic interventions such as anti-CTLA4 therapy can exert clinically effects. However, there is very little information on how these therapies influence tumor-specific T cell responses. Furthermore, as the number of potential melanoma-associated antigens...
Article
9085 Background: Evidence for T cell mediated regression of human cancer in particular melanoma following immunotherapy is strong. Anti-CTLA4 treatment has been approved for treatment of metastatic melanoma and blockade of PD-1 has shown encouraging results. However, it is unknown which T cell reactivities are involved in cancer regression. Reactiv...
Article
Full-text available
Cancer cells deviate from normal body cells in two immunologically important ways. First, tumour cells carry tens to hundreds of protein-changing mutations that are either responsible for cellular transformation or that have accumulated as mere passengers. Second, as a consequence of genetic and epigenetic alterations, tumour cells express a series...
Article
Full-text available
There is strong evidence that both adoptive T cell transfer and T cell checkpoint blockade can lead to regression of human melanoma. However, little data are available on the effect of these cancer therapies on the tumor-reactive T cell compartment. To address this issue we have profiled therapy-induced T cell reactivity against a panel of 145 mela...
Article
Abbreviations: CTL, cytotoxic T lymphocyte; MM, malignant melanoma; TILs, tumor-infiltrating lymphocytes