Immunotherapy is a type of treatment that harnesses the power of our own immune system to treat cancer. In a last decade, cancer immunotherapy become a foundation for cancer treatment approved for more than a dozen types of cancer, but it comes with its own challenge as not all cancer immunotherapies work for all patients.
Immune checkpoint targets
Immune checkpoint inhibitors (ICB), the most common type of immunotherapy targeting PD(L)-1 and CTLA-4 typically elicits durable response only in a subset of patients (20-40%) with solid tumors. Majority of patients either do not respond to immunotherapy, acquire resistance, or are limited by treatment related immune toxicities. Predicting response to ICB remains a challenge and improving our understanding of response biology and mechanism of resistance become increasingly important. Due to the complex relationship between dynamic nature of the host immune system and tumor biology, combined efforts and tools are required to accelerate research and design better treatment options essential to expand benefits of immunotherapy for non-responding patients beyond the success of current ICB.
Accelerating progress in cancer immunotherapy
Predictive biomarkers remain rapidly emerging area of research in immunotherapy. In recent years, development of minimally invasive and robust liquid biopsy-based biomarkers become urgently needed. Several liquid biopsy targets including ctDNA and CTC are currently under investigation as a promising marker for treatment response. While proteins represent an important liquid biopsy target with the ability to characterize the activity of a patient’s immune system and their tumor, assessment and the utility circulating proteins for immunotherapy is largely unexplored due to the lack of technological advances.
Proteomic Profiling in Melanoma Immunotherapy: This study, carried out in collaboration with the Massachusetts General Hospital Cancer Center, performed deep proteomic profiling together with single-cell RNAseq in a metastatic melanoma cohort during ICB treatment. The results demonstrate the utility of blood-based protein biomarkers to predict treatment response and reveals that response proteins were enriched in tumor myeloid cells and implicated in mechanism of resistance to ICB treatment. The study initially looked at >700 proteins using Olink Target 96 panels and then examined ~1500 proteins with the Olink Explore 1536 platform in an extended cohort.
You may also be interested to see an interview with Dr. Genevieve Boland, who led this study, which was published in Select Science – view the article here.
Some examples of how Olink panels have been used in the field of cancer immunotherapy have been presented in a Science/AAAS webinar, “Emerging liquid biopsy biomarkers: Predicting response and resistance to cancer immunotherapy“.
This was originally broadcast on 9th October 2019, featuring Genevieve Boland, M.D., Ph.D., FACS Massachusetts General Hospital, Boston, MA and Evert Jan Van Limbergen, M.D., Ph.D.Maastro Clinic Maastricht, The Netherlands. Click here to register and access the on-demand recording of these presentations.
Olink in immunotherapy research
Olink’s solutions for protein biomarker discovery (Olink Explore 1536 and Olink Target 96 panels) are being increasingly used in immunotherapy studies across different tumor types and different immunotherapy treatment strategies and settings. These include:
Predict and monitor treatment response, patient stratification
Tumor biology insight, mechanism of immune modulation, phenotype changes, transformation cold to hot tumors
Clarify the interconnected roles of tumor genomics, transcriptomics and proteomics in predicting response to immunotherapy
Treatment sensitivity and mechanism of immune resistance, design of strategies to optimize response rates and identify novel targetable pathways
Assess the longitudinal biomarker changes between early timepoints (baseline to treatment) and later timepoints (baseline to disease progression) to identify key markers associated with the transition from a drug-sensitive to drug-resistant state
Explore the association between baseline circulating immune proteins and patient outcome (OS and PFS)
Predict onset and mechanism of treatment associated toxicity, monitoring CRS and neurotoxicity
Predict recurrence and on-treatment progression in adjuvant settings
“Our work with Olink on plasma-based immuno-oncology (IO) applications has allowed the identification of tumor and immune changes associated with immune checkpoint inhibitor response/non-response.This is particularly exciting as we combine this technology with deep tumor-based analysis to understand tumor-immune interactions and establish predictive and/or monitoring tools for IO. The small volume required for Olink analysis is a game-changer as it allows multi-analyte assessment of samples and validation of findings by multiple orthogonal platforms.”
Genevieve M. Boland, Director Melanoma Surgery Program, Massachusetts General Hospital, Boston
More examples of immunotherapy studies using Olink
Collaborative research initiatives
The Cancer Immune Monitoring and Analysis Centers-Cancer Immunologic Data Commons (CIMAC-CIDC) Network was launched in 2017 through the Cancer MoonshotSM initiative supported by the NCI, and collaborates with another Cancer Moonshot project, the Partnership for Accelerating Cancer Therapies (PACT). Olink has been chosen as the core assay for profiling of cytokines, chemokines, and growth factors within this project, as reported in a recent article from CIMAC-CIDC/PACT:
Chen et al (2021) Clin. Cancer Res, DOI: 10.1158/1078-0432.CCR-20-3241 – article link
You can also read more about this important initiative for cancer immunotherapy research at the CIMAC-CIDC website
Maastricht University Medical Center
An exploratory prospective study, performed in collaboration with Maastricht University Medical Center, investigated circulating biomarkers of immunogenic cell death (ICD) after radiotherapy and chemotherapy in stage III NSCLC and identified important changes in immune protein profile. The overarching goal in on-going follow up prospective study is to improve therapeutic efficacy of immunotherapy in stage III NSCLC patients treated with concurrent chemotherapy and photon or proton radiotherapy and adjuvant durvalumab (anti-PD-L1). Some of this work will be presented at AACR 2021, in a presentation entitled, “Biomarkers in Radiotherapy” that will be held in the session “Advances in Diagnostics and Therapeutics Session Proton Therapy and FLASH Irradiation” on Monday, April 12, 2021.
“To exploit immunotherapy for cancer optimally, biomarkers are essential for, they will lead to personalized selection of the best treatment during the course of the disease. Blood biomarkers are ideal in this respect as they allow repeated sampling and avoid sampling heterogeneity within the tumor and between tumor locations in the same patient as is the case with tumor biopsies.”
Dr. Dirk de Ruysscher, Professor of Respiratory Oncology, Maastricht University Medical Center, Maastro Clinic, Netherlands
The joint Olink/customer poster, “Liquid biopsy protein biomarkers to predict responses and elucidate resistance to cancer immunotherapy” by Rucevic et al was presented at the Society for Immunotherapy of Cancer (SITC) meeting in National Harbor, MD in November 2019.
You are very welcome to download and read the poster – DOWNLOAD HERE
Selected publications citing Olink in cancer immunotherapy studies
Babačić H, Lehtiö J, Pico de Coaña Y, Pernemalm M and Eriksson H. In-depth plasma proteomics reveals increase in circulating PD-1 during anti-PD-1 immunotherapy in patients with metastatic cutaneous melanoma. (2020) Journal for ImmunoTherapy of Cancer, DOI: 10.1136/jitc-2019-000204 Article link>
Kasanen H, Hernberg M, Mäkelä S, Brück O, Juteau S, Kohtamäki L, Ilander M, Mustjoki S and Kreutzman A. Age-associated changes in the immune system may influence the response to anti-PD1 therapy in metastatic melanoma patients. (2020) Cancer Immunology, Immunotherapy, DOI: 10.1007/s00262-020-02497-9 Article link>
Pedersen JG, Madsen AT, Gammelgaard, KR, et. al. Inflammatory Cytokines and ctDNA Are Biomarkers for Progression in Advanced-Stage Melanoma Patients Receiving Checkpoint Inhibitors. (2020) Cancers, DOI: /10.3390/cancers12061414 Article link>
Taylor M, HugheRs A, Walton J, Coenen-Stass A, Magiera L, Mooney L, Bell S, Staniszewska A, Sandin L, Barry S, Watkins A, Carnealli L and Hardaker E. (2019) Longitudinal immune characterization of syngeneic tumor models to enable model selection for immune oncology drug discovery. Journal for Immunotherapy of Cancer, DOI: 10.1186/s40425-019-0794-7
Enblad G, Karlsson H, Gammelgård G, Wenthe J, Lövgren T, Amini M, Wikstrom K, Essand M, Savoldo B, Hallböök H, Höglund M, Dotti G, Brenner M, Hagberg H and Loskog A. (2018) A Phase I/IIa Trial Using CD19-Targeted ThirdGeneration CAR T Cells for Lymphoma and Leukemia. Clinical Cancer Research, doi: 10.1158/1078-0432.CCR-18-0426 Article link>