Immune Biomarker Study for Salivary Gland Carcinoma (ImmoGlandula)

Salivary gland carcinomas (SGC) are rare tumors. The term SGC is not more than an umbrella for a variety of histogenetically, morphologically, and biologically distinct entities. Accordingly, SGCs have not been sufficiently investigated to date. Their rarity makes it challenging to recruit a high number of patients for individual entities in clinical studies, leading to the pooling of patients with different histological subtypes to achieve sufficient participants. The different histological subtypes of SGC exhibit significant differences in their clinicopathological features, including grading, occurrence, and outcome. SGCs usually are stratified into low-, intermediate-, or high-grade tumors. In most kinds of SGC, specific targetable molecular markers are lacking. The inclusion of immunotherapy (IT), however, might improve the outcome of patients suffering from high-grade SGCs. To integrate IT as a therapeutic option for SGC and to facilitate informed therapeutic decisions based on tumor (immune) biology, predictive and prognostic immunological biomarkers are indispensable. In this prospective study, 500 patients will be enrolled, distributed across three arms. The observational cohort includes patients with malignant salivary gland tumors, whereas patients with benign tumors of a salivary gland are grouped in the control group 1. In the control cohort, two patients do not have a salivary gland tumor but have a planned functional surgery of the nose or ear or a maxillofacial surgery. The local immune status of the tumor tissue and the microbiome will be sampled before treatment. In addition, the systemic immune status from peripheral blood will be analyzed before and after surgery and after the adjuvant and definitive chemoradiotherapy (CRT), if applicable. Clinical baseline characteristics and outcome parameters will additionally be collected. Data mining and modeling approaches will be applied to identify interactions between local and systemic immune parameters and to define predictive and prognostic immune signatures based on the evaluated immune markers.

Study Overview

• Status: Recruiting
• Conditions: Salivary Gland Tumor; Benign Salivary Gland Tumor
• Intervention / Treatment: Other: Sampling

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Studiensekretariat; Phone Number: 43921 +49913185; Email: studiensekretariat.ST@uk-erlangen.de
• Study Contact Backup: Name: Translation Radiobiology; Phone Number: 44925 +49913185; Email: Anna-Jasmina.Donaubauer@uk-erlangen.de

Study Locations

• Germany
  • Bavaria
    • Erlangen, Bavaria, Germany, 91054
      • Recruiting
      • Universitätsklinikum Erlangen, Strahlenklinik
      • Contact: Marlen Haderlein, PD; Phone Number: 33968 +49913185; Email: marlen.haderlein@uk-erlangen.de
    • Erlangen, Bavaria, Germany, 91054
      • Recruiting
      • Universitätsklinikum Erlangen, HNO
      • Contact: Sarina Mueller, PD; Phone Number: 43921 +49-9131-85; Email: sarina.mueller@uk-erlangen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients presenting for treatment at the participating study centers and meeting the inclusion criteria.

Description

Inclusion Criteria:

1. Observational group

   • Initial diagnosis of a primary salivary gland carcinoma in the head and neck region (no squamous cell carcinomas)
   • Specimen collection from the center of the tumor when the primary tumor is sufficiently large without that the pathological assessment is impaired

2. Control group 1

   • Initial diagnosis of a benign salivary gland tumor in the head and neck region
   • Specimen collection from the center of the tumor when the primary tumor is sufficiently large without that the pathological assessment is impaired

3. Control group 2

   • functional diseases of the nose or ear (patients with the indication for functional ear surgery and rhinoplasty)
   • Specimen collection with sufficiently large resectate during a functional nose surgery

for all groups:

• Willingness of patients to collect blood, saliva and stool and consent to the preservation of all samples for study purposes.
• Age ≥ 18 years
• sufficient cognitive ability of the patients to understand the purpose of the study and to understand the purpose of the study and agree to it

Exclusion Criteria:

• Distant metastasis at the time of diagnosis and simultaneous second cancers, i.e. at study inclusion
• Malignancy in the last 5 years regardless of location (except basal cell carcinoma or cis of the uterine cervix)
• Carcinomas for which specimen collection is not possible or likely without compromising the compromise the pathological evaluation
• Persistent drug or medication abuse
• Patients who are unable or unwilling to comply with protocol and to be treated
• Patients who are represented by a legal guardian
• Patients who are not suitable for participation in the study due to a language barrier

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Malignant salivary gland tumor in the head and neck region; Initial diagnosis of primary salivary gland carcinoma in the head and neck region	Other: Sampling; Evaluation of immune characteristics by using patient's stool, saliva, blood, and tumour (not in control group 2) samples.
Benign salivary gland tumor in the head and neck region; Initial diagnosis of a benign salivary gland tumor in the head and neck region	Other: Sampling; Evaluation of immune characteristics by using patient's stool, saliva, blood, and tumour (not in control group 2) samples.
functional disorders of the nose or ear; Healthy control group. Functional diseases of the nose or ear (patients with the indication for functional ear surgery and rhinoplasty) without salivary gland tumor.	Other: Sampling; Evaluation of immune characteristics by using patient's stool, saliva, blood, and tumour (not in control group 2) samples.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	As a primary clinical endpoint, the progression-free survival (PFS) of the patients in the observational cohort will be analyzed after two years.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Locoregional recurrence rate (LRR)	Secondary clinical endpoints, the locoregional recurrence rate (LRR) after two and five years in the observational cohort will be addressed.	From baseline to the end of study period, up to 5 years
Occurrence of distant metastases	The occurrence of distant metastases after two and five years in the observational cohort will be addressed.	From baseline to the end of study period, up to 5 years
Longitudinal immunophenotyping of the patients: Detection of about 30 distinct immune cell (sub)types together with their activation markers during study period	The distribution of immune cells and messenger substances in the blood will be examined by means of immunophenotyping in order to add the systemic immune cell composition. Flow cytometric assessment of the amount of circulating immune cell-distribution per milliliter whole blood.	Change of the immunophenotyping from baseline to the end of study period, up to 5 years
Immune status of the resected tumor	The local immune status of the resected tumor is assessed by examining various immunological parameters during the pathological analysis of the tissue, which includes the expression of immune checkpoint molecules on the cells of the tumor microenvironment, such as PD1, its respective ligands or TIM3 and LAG3. Further, the infiltration of numerous of different immune cell populations in the tumor tissue will be examined, which includes CD19+ CD20+ B cells, CD4+ and CD8+ T cells or neutrophilic granulocytes.	1 year
Transcriptional changes in immune cell gene expression	Blood is also drawn into RNA stabilization tubes to create cell lysates for long-term storage and to isolate total RNA from blood cells. Cell pellets from whole blood are preserved for the extraction of nucleic acids. The collection and storage of biomaterials are managed by the Central Biobank Erlangen (CeBE). Transcriptional analyses will be conducted using whole-exome sequencing, RNA sequencing, digital droplet PCR, or real-time quantitative PCR.	Change of the immunophenotyping from baseline to the end of study period, up to 5 years
Analysis of patient's microbiomic state by examination of saliva, tumor and stool	For the microbiome analysis, stool, saliva, and tumor smear samples are collected preoperatively (stool and saliva) and after the tumor excision (tumor smear). The composition of the oral, bowel, and tumor microbiome is determined through metagenomic analyses to identify all non-human species present in the samples. The qualitative and quantitative diversity of the microbiome is then evaluated using bioinformatics approaches.	The analyses are conducted from baseline to the end of study period, up to 5 years
Analysis of cytokines and metabolites in peripheral blood and their change at certain points in the course of treatment	Electrochemiluminescent MULTI-ARRAY measurement of concentration (pg/ml whole blood) cytokines/chemoattractant cytokines in the serum/plasma of the patients. Mass spectrometry will be employed to analyze changes in metabolites from the serum and plasma.	Change of the cytokine expression from baseline to the end of study period, up to 5 years

Collaborators and Investigators

• Sponsor: University of Erlangen-Nürnberg Medical School
• Investigators: Study Director: Sarina Mueller, PD, Universitätsklinikum Erlangen, HNO; Study Director: Marlen Haderlein, PD, Universitätsklinikum Erlangen, Radiation Oncology; Principal Investigator: Benjamin Frey, PD, Universitätsklinikum Erlangen, Radiation Oncology, Translational Radiobiology

Publications and helpful links

General Publications

• Donaubauer AJ, Ruhle PF, Becker I, Fietkau R, Gaipl US, Frey B. One-Tube Multicolor Flow Cytometry Assay (OTMA) for Comprehensive Immunophenotyping of Peripheral Blood. Methods Mol Biol. 2019;1904:189-212. doi: 10.1007/978-1-4939-8958-4_8.
• Donaubauer AJ, Becker I, Ruhle PF, Fietkau R, Gaipl US, Frey B. Analysis of the immune status from peripheral whole blood with a single-tube multicolor flow cytometry assay. Methods Enzymol. 2020;632:389-415. doi: 10.1016/bs.mie.2019.03.003. Epub 2019 Apr 4.
• Zhou JG, Donaubauer AJ, Frey B, Becker I, Rutzner S, Eckstein M, Sun R, Ma H, Schubert P, Schweizer C, Fietkau R, Deutsch E, Gaipl U, Hecht M. Prospective development and validation of a liquid immune profile-based signature (LIPS) to predict response of patients with recurrent/metastatic cancer to immune checkpoint inhibitors. J Immunother Cancer. 2021 Feb;9(2):e001845. doi: 10.1136/jitc-2020-001845.
• Hiss S, Eckstein M, Segschneider P, Mantsopoulos K, Iro H, Hartmann A, Agaimy A, Haller F, Mueller SK. Tumour-Infiltrating Lymphocytes (TILs) and PD-L1 Expression Correlate with Lymph Node Metastasis, High-Grade Transformation and Shorter Metastasis-Free Survival in Patients with Acinic Cell Carcinoma (AciCC) of the Salivary Glands. Cancers (Basel). 2021 Feb 25;13(5):965. doi: 10.3390/cancers13050965.
• Freitag V, Lettmaier S, Semrau S, Hecht M, Mantsopoulos K, Muller SK, Traxdorf M, Iro H, Agaimy A, Fietkau R, Haderlein M. High-grade salivary gland cancer: is surgery followed by radiotherapy an adequate treatment to reach tumor control? Results from a tertiary referral centre focussing on incidence and management of distant metastases. Eur Arch Otorhinolaryngol. 2022 May;279(5):2553-2563. doi: 10.1007/s00405-021-07024-9. Epub 2021 Aug 26.
• Haderlein M, Scherl C, Semrau S, Lettmaier S, Uter W, Neukam FW, Iro H, Agaimy A, Fietkau R. High-grade histology as predictor of early distant metastases and decreased disease-free survival in salivary gland cancer irrespective of tumor subtype. Head Neck. 2016 Apr;38 Suppl 1:E2041-8. doi: 10.1002/hed.24375. Epub 2016 Feb 3.
• Donaubauer AJ, Frey B, Agaimy A, Lange F, Mogge L, Fietkau R, Iro H, Munoz LE, Weber M, Kesting M, Gaipl US, Haderlein M, Muller S. Definition of predictive and prognostic immune biomarkers for salivary gland cancer from the intratumoural and systemic immune status: detailed protocol of the prospective, observatory ImmoGlandula study. BMJ Open. 2026 Jan 12;16(1):e100021. doi: 10.1136/bmjopen-2025-100021.

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2024
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): September 30, 2031

Study Registration Dates

• First Submitted: September 14, 2023
• First Submitted That Met QC Criteria: September 14, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Salivary Gland Diseases; Mouth Neoplasms; Salivary Gland Neoplasms
• Other Study ID Numbers: ImmoGlandula

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No