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. 2025 Mar 7;13(3):e010928.
doi: 10.1136/jitc-2024-010928.

Society for Immunotherapy of Cancer (SITC) consensus statement on essential biomarkers for immunotherapy clinical protocols

Tricia R Cottrell  1 , Michael T Lotze  2 , Alaa Ali  3 , Carlo B Bifulco  4 , Christian M Capitini  5 , Laura Q M Chow  6 , Anthony R Cillo  2   7 , Deborah Collyar  8 , Leslie Cope  9 , Julie Stein Deutsch  10 , Genia Dubrovsky  2 , Sacha Gnjatic  11 , Denise Goh  12 , Susan Halabi  13 , Gary Kohanbash  7   14 , Holden T Maecker  15 , Saman Maleki Vareki  16 , Sarah Mullin  17 , Barbara Seliger  18 , Janis Taube  10 , Wim Vos  19 , Joe Yeong  12   20 , Kristin G Anderson  21 , Tullia C Bruno  2   7   22   23 , Codruta Chiuzan  24 , Ivan Diaz-Padilla  25 , Elizabeth Garrett-Mayer  26 , Isabella C Glitza Oliva  27 , Paola Grandi  28 , Elizabeth G Hill  29 , Brian P Hobbs  30 , Yana G Najjar  2 , Phyllis Pettit Nassi  31 , Virgil H Simons  32 , Sumit K Subudhi  27 , Ryan J Sullivan  33 , Chris H Takimoto  34
Affiliations

Society for Immunotherapy of Cancer (SITC) consensus statement on essential biomarkers for immunotherapy clinical protocols

Tricia R Cottrell et al. J Immunother Cancer. .

Abstract

Immunotherapy of cancer is now an essential pillar of treatment for patients with many individual tumor types. Novel immune targets and technical advances are driving a rapid exploration of new treatment strategies incorporating immune agents in cancer clinical practice. Immunotherapies perturb a complex system of interactions among genomically unstable tumor cells, diverse cells within the tumor microenvironment including the systemic adaptive and innate immune cells. The drive to develop increasingly effective immunotherapy regimens is tempered by the risk of immune-related adverse events. Evidence-based biomarkers that measure the potential for therapeutic response and/or toxicity are critical to guide optimal patient care and contextualize the results of immunotherapy clinical trials. Responding to the lack of guidance on biomarker testing in early-phase immunotherapy clinical trials, we propose a definition and listing of essential biomarkers recommended for inclusion in all such protocols. These recommendations are based on consensus provided by the Society for Immunotherapy of Cancer (SITC) Clinical Immuno-Oncology Network (SCION) faculty with input from the SITC Pathology and Biomarker Committees and the Journal for ImmunoTherapy of Cancer readership. A consensus-based selection of essential biomarkers was conducted using a Delphi survey of SCION faculty. Regular updates to these recommendations are planned. The inaugural list of essential biomarkers includes complete blood count with differential to generate a neutrophil-to-lymphocyte ratio or systemic immune-inflammation index, serum lactate dehydrogenase and albumin, programmed death-ligand 1 immunohistochemistry, microsatellite stability assessment, and tumor mutational burden. Inclusion of these biomarkers across early-phase immunotherapy clinical trials will capture variation among trials, provide deeper insight into the novel and established therapies, and support improved patient selection and stratification for later-phase clinical trials.

Keywords: Biomarker; Dendritic; Immunotherapy; Neutrophil; T cell.

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Conflict of interest statement

Competing interests: TRC—Consulting Fees: Jannsen; MTL—Ownership Interest: iRepertoire; Consulting Fees: iRepertoire; KSQ; BioCytics; Zia Pharma; KSQ Therapeutics, Appel Sauce (pending); Agenus (pending); AA—Nothing to disclose; CBB—Owner: PrimeVax; Researcher: Illumina; Consultant Advisor Speaker: Sanofi, Agilent, Roche, Incendia, PrimeVax, BioAI, Lunaphore, SironaDx; CMC—Consultant Advisor Speaker: Bayer, Elephas, Novartis, Nektar Therapeutics, WiCell Research Institute; LQMC—Employee: Summit Therapeutics November 1, 2023 to January 2024. Previously Fate Therapeutics October 2022 to October 2023; Owner: LQMC Oncology Strategies PLLC; Researcher: Oncorus; Independent Contractor: Tallac Therapeutics, ALX Oncology, CytomX Therapeutics, Scailyte AG; Individually publicly traded stocks and stock options: Fate Therapeutics; ARC—Consultant Advisor Speaker: Abound Bio; DC—Executive Role: Metastatic Breast Cancer Alliance; Consultant Advisor Speaker: Parexel, MaxisIT Clinical Sciences, Kinnate Biopharma, Apellis Pharmaceuticals, Incyte, SimBioSys, Aster Insights, Evidera, AstraZeneca, Health Literacy Media (non-profit); LC—Nothing to disclose; JSD—Nothing to disclose; GD—Nothing to disclose; SG—Grant Funding to Institution: Regeneron, Boehringer Ingelheim, Janssen R&D, Genentech, Takeda, Bristol Myers Squibb, Celgene; Patents: Co-inventor on an issued patent for multiplex immunohistochemistry to characterize tumors and treatment responses. The technology is filed through Icahn School of Medicine at Mount Sinai (ISMMS) and is currently unlicensed, Inventor of technology to detect autoantibodies to GM-CSF, a cytokine that promotes myeloid cell development and maturation. The technology is filed through ISMMS and is currently unlicensed, Inventor on a patent application “NY-ESO-1 Polypeptides†filed through Mount Sinai and Ludwig Institute. This technology is currently unlicensed.; DG—Nothing to disclose; SH—DSMB: Aveo Oncology, Beigene, BMS, CC Oncology, Janssen, Sanofi; Research Funding: ASCO Astellas; HTM—Consulting Fees: Caris Life Sciences, Cytek Biosciences; Stock Holdings: Caris Life Sciences, Cytek Biosciences; SMV—Consultant Advisor Speaker: Fed Bio, Vedanta Biosciences, Advention Business partners, Kanvas Bio; Other: IMV (Former Board member); GK—Nothing to disclose; SM—Other: Husband owner/stocks (Amritx, not publicly traded significant obligation and equity; Meditati, not publicly traded significant obligation and equity; both are start-up bioinformatics companies. They do not deal with immunotherapies.); JY— Nothing to disclose; BS—Nothing to disclose; JT—Researcher: Bristol Myers Squibb; Akoya Biosciences; Consultant Advisor Speaker: Bristol Myers Squibb; Roche/Genentech; Merck & Co; AstraZeneca; Regeneron; Lunaphore; Akoya Biosciences; Compugen; Publicly Traded Stocks: Akoya Biosciences; Other: Akoya Biosciences (Equipment loan and provision of reagents from Akoya Biosciences); WV—Owner: Radiomics; Executive Role: Radiomics (CEO), Nomics; Independent Contractor: Radiomics; Shareholder: Radiomics; KGA—Executive Role: Powell-Drescher Ovarian Cancer Research Foundation; Consultant Advisor Speaker: Society for Immunotherapy of Cancer (SITC); TCB—Employee: Tabby Therapeutics, Genmab, Galvanize, Attivare, Mestag, KaliVir; CC—Nothing to disclose; ID-P—Employee: GSK; Shareholder: GSK; EG-M—Nothing to disclose; ICGO—Researcher: BMS, Merck, Pfizer; Consultant Advisor Speaker: Novartis, BMS, Leal Therapeutics, Pfizer, Biodexa, Enclear Therapeutics, Candel Therapeutics; PG—Employee: CG Oncology; Owner: CG Oncology shareholder; Executive Role: CGO Oncology CSO; EGH—Nothing to disclose; BPH—Owner: Telperian; Consultant Advisor Speaker: Amgen, CSL Behring, Sana Biotechnology; YGN—Researcher: Merck, Pfizer, BMS, Replimune; Consultant Advisor Speaker: Novartis, Merck, InterVenn Biosciences, Pfizer, Immunocore, BMS; PPN—Nothing to disclose; VHS—Executive Role: Founder and President The Prostate Net; Consultant Advisor Speaker: NCI-funded CaRE2PC Program; Mt Sinai (NYC) Cancer Center External Advisory Board; University of Wisconsin Prostate SPORE External Advisory Board; University of Florida; Publicly Traded Stocks: Bayer AG, Sanofi, NightHawk Biosciences, Berkshire Hathaway, Benchmark Electronics; SKS—Researcher: AstraZeneca, Bristol Myers Squibb, Janssen and Regeneron; Consultant Advisor Speaker: Biosciences, Baird, Bayer, Boxer Capital, Breaking Data, Bristol Myers Squibb, Cancer Expert Now, ChemoCentryx, Dendreon, InProTher, Janssen, Javelin Oncology, Kahr Medical, Kiniksa Pharmaceuticals, MD Education Limited, Macrogenics, Merck, OncLive (owned by Intellisphere, LLC), Pfizer, Portage, Regeneron, Rondo Therapeutics, and The Clinical Comms Group; Other: Bristol Myers Squibb, Janssen, Polaris and Regeneron (Joint Scientific Committee); RJS—Researcher: Merck (research funding); Consultant Advisor Speaker: BMS, Merck, Novartis, Pfizer, Marengo; CHT—Employee: IGM Biosciences; Executive Role: IGM Biosciences, Chief Medical Officer; Publicly Traded Stocks: IGMS, JNJ, GILD; SITC Staff (Peter J Intile, PhD, Eleanor (Ellie) Rickman)—Nothing to disclose.

Figures

Figure 1
Figure 1. Essential, eligibility, and emergent biomarkers for early-phase immunotherapy clinical trials. Biomarker testing performed on peripheral blood, tumor tissue, and other biospecimens or imaging data (red) provides insight into the interacting systems of cancer cells, the tumor microenvironment, and the patient’s immune system that dictate immunotherapy outcomes. Essential biomarkers (blue) were selected based on strong evidence of biological and/or clinical relevance across tumor types as well as high feasibility for testing (see also box 1, table 2). Essential biomarkers also include tumor-specific biomarkers that are used in routine clinical care. A subset of essential biomarkers, eligibility (or integral) biomarkers are incorporated into the design of a clinical trial, that is, required for patient enrollment. Emergent (or exploratory) biomarkers (green) have early evidence of biological and/or clinical relevance but may be limited by a lack of standardization or data across tumor types (see also tables2 3). AI, artificial intelligence; β2M, β2-microglobulin; BCRseq, T cell receptor sequencing; CBC, complete blood count; ctDNA, circulating tumor DNA; IF, immunofluorescence; IHC, immunohistochemistry; LDH, lactate dehydrogenase; MHC, major histocompatibility complex; MSI, microsatellite instability; NLR, neutrophil-to-lymphocyte ratio; PD-L1, programmed death-ligand 1; SII, systemic immune-inflammation index; TCRseq, T cell receptor sequencing; TMB, tumor mutational burden; TME, tumor microenvironment.
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References

    1. Hellström I, Sjögren HO, Warner G, et al. Blocking of cell-mediated tumor immunity by sera from patients with growing neoplasms. Int J Cancer. 1971;7:226–37. doi: 10.1002/ijc.2910070206. - DOI - PubMed
    1. Hellström I, Hellström KE. Can 'blocking' serum factors protect against autoimmunity? Nature New Biol. 1972;240:471–3. doi: 10.1038/240471a0. - DOI - PubMed
    1. Hellstrom KE, Hellstrom I. From the Hellstrom paradox toward cancer cure. Prog Mol Biol Transl Sci. 2019;164:1–24. doi: 10.1016/bs.pmbts.2018.11.002. - DOI - PubMed
    1. Angelova M, Mlecnik B, Vasaturo A, et al. Evolution of Metastases in Space and Time under Immune Selection. Cell. 2018;175:751–65. doi: 10.1016/j.cell.2018.09.018. - DOI - PubMed
    1. Matsushita H, Vesely MD, Koboldt DC, et al. Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting. Nature New Biol. 2012;482:400–4. doi: 10.1038/nature10755. - DOI - PMC - PubMed

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