Effects of Acute and Chronic Exercise on Myeloid-Derived Suppressor Cells in Melanoma Patients

NCT05615883 | Completed DMC

• 2 other identifiers: INT 148/19IG 2017 Project n. 20752
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to investigate the effects of ketogenic milieu induced by acute exercise as well as the effects of recurrent exercise bouts on functional status and the accumulation in peripheral blood of MDSCs and the consequent balance on antitumor immunity in melanoma patients.

Conditions

Melanoma

Keywords

Primary Melanoma

Outcome Measures

Primary Outcomes (64)

• Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise)

  Immune cells will be analyzed for frequency and function by 10-color flow cytometry to test the reciprocal balance of protumor vs antitumor immune subsets. The analysis, based in the application of multiple panels of different antibodies, will be performed on peripheral blood mononuclear cells (PBMC) isolated from peripheral blood.

  AEP group: before exercise session.

• Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise)

  Immune cells will be analyzed for frequency and function by 10-color flow cytometry to test the reciprocal balance of protumor vs antitumor immune subsets. The analysis, based in the application of multiple panels of different antibodies, will be performed on peripheral blood mononuclear cells (PBMC) isolated from peripheral blood.

  AEP group: after 40 minutes of exercise session.

• Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise)

  Immune cells will be analyzed for frequency and function by 10-color flow cytometry to test the reciprocal balance of protumor vs antitumor immune subsets. The analysis, based in the application of multiple panels of different antibodies, will be performed on peripheral blood mononuclear cells (PBMC) isolated from peripheral blood.

  AEP group: after 80 minutes of exercise session.

• Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise)

  Immune cells will be analyzed for frequency and function by 10-color flow cytometry to test the reciprocal balance of protumor vs antitumor immune subsets. The analysis, based in the application of multiple panels of different antibodies, will be performed on peripheral blood mononuclear cells (PBMC) isolated from peripheral blood.

  AEP group: at 24 post-exercise.

• Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise)

  Immune cells will be analyzed for frequency and function by 10-color flow cytometry to test the reciprocal balance of protumor vs antitumor immune subsets. The analysis, based in the application of multiple panels of different antibodies, will be performed on peripheral blood mononuclear cells (PBMC) isolated from peripheral blood.

  AEP group: at 72 hours post-exercise.

• Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise)

  Immune cells will be analyzed for frequency and function by 10-color flow cytometry to test the reciprocal balance of protumor vs antitumor immune subsets. The analysis, based in the application of multiple panels of different antibodies, will be performed on peripheral blood mononuclear cells (PBMC) isolated from peripheral blood.

  CEP group: before exercise program.

• Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise)

  Immune cells will be analyzed for frequency and function by 10-color flow cytometry to test the reciprocal balance of protumor vs antitumor immune subsets. The analysis, based in the application of multiple panels of different antibodies, will be performed on peripheral blood mononuclear cells (PBMC) isolated from peripheral blood.

  CEP group: after one week of exercise program.

• Quantification of the immune cell subsets (to determine if occur the re-setting antitumor immunity by short-term physical exercise)

  Immune cells will be analyzed for frequency and function by 10-color flow cytometry to test the reciprocal balance of protumor vs antitumor immune subsets. The analysis, based in the application of multiple panels of different antibodies, will be performed on peripheral blood mononuclear cells (PBMC) isolated from peripheral blood.

  CEP group: up to two weeks of exercise program.

• Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise)

  CD14+, CD15+ and total immune cells will be immunosorted directly from whole blood (3 ml) and frozen for the targeted expression profiling of signaling pathways and functional patterns (Nanostring or customized PCR cards).

  AEP group: before exercise.

• Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise)

  CD14+, CD15+ and total immune cells will be immunosorted directly from whole blood (3 ml) and frozen for the targeted expression profiling of signaling pathways and functional patterns (Nanostring or customized PCR cards).

  AEP group: after 40 minutes of exercise session

• Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise)

  CD14+, CD15+ and total immune cells will be immunosorted directly from whole blood (3 ml) and frozen for the targeted expression profiling of signaling pathways and functional patterns (Nanostring or customized PCR cards).

  AEP group: after 80 minutes of exercise session.

• Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise)

  CD14+, CD15+ and total immune cells will be immunosorted directly from whole blood (3 ml) and frozen for the targeted expression profiling of signaling pathways and functional patterns (Nanostring or customized PCR cards).

  AEP group: at 24 post-exercise.

• Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise)

  CD14+, CD15+ and total immune cells will be immunosorted directly from whole blood (3 ml) and frozen for the targeted expression profiling of signaling pathways and functional patterns (Nanostring or customized PCR cards).

  AEP group: at 72 hours post-exercise.

• Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise)

  CD14+, CD15+ and total immune cells will be immunosorted directly from whole blood (3 ml) and frozen for the targeted expression profiling of signaling pathways and functional patterns (Nanostring or customized PCR cards).

  CEP group: before exercise program.

• Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise)

  CD14+, CD15+ and total immune cells will be immunosorted directly from whole blood (3 ml) and frozen for the targeted expression profiling of signaling pathways and functional patterns (Nanostring or customized PCR cards).

  CEP group: after one week of exercise program.

• Transcriptional Immune cell profiling (to determine if occur the re-setting antitumor immunity by short-term physical exercise)

  CD14+, CD15+ and total immune cells will be immunosorted directly from whole blood (3 ml) and frozen for the targeted expression profiling of signaling pathways and functional patterns (Nanostring or customized PCR cards).

  CEP group: up to two weeks of exercise program.

• Analysis of the "systemic metabolic milieu"_AEPMet before

  In plasma we will quantify pH, Lactate, Ketone bodies, Free Fatty Acids, Glucose and Insulin serum levels that will be combined to report the metabolic parameters

  AEP group: before exercise.

• Analysis of the "systemic metabolic milieu"_AEPHor before

  In serum we will quantify ACTH, cortisol, epinephrine and norepinephrine concentrations that will be combined to report the hormonal parameters

  AEP group: before exercise.

• Analysis of the "systemic metabolic milieu"_AEPInf before

  In blood we will quantify IL-6, CRP, inflammatory cito/chemokines such as IL8, CCL2, IFN, IL10, IL1b, TNFa, TGFb that will be combined to report the inflammatory parameters

  AEP group: before exercise.

• Analysis of the "systemic metabolic milieu"_AEPLip before

  We will analyze the Lipidomics and amino acid profiles by laboratory test that will be combined to report the composition of cell membranes

  AEP group: before exercise.

• Analysis of the "systemic metabolic milieu"_AEPcounts before

  Whole blood cell counts will be also performed; this parameter is characterized by the absolute number as well as relative ratio.

  AEP group: before exercise.

• Analysis of the "systemic metabolic milieu"_AEPMet 40

  In plasma we will quantify pH, Lactate, Ketone bodies, Free Fatty Acids, Glucose and Insulin serum levels that will be combined to report the metabolic parameters

  AEP group: after 40 minutes of exercise session.

• Analysis of the "systemic metabolic milieu"_AEPHor 40

  In serum we will quantify ACTH, cortisol, epinephrine and norepinephrine concentrations that will be combined to report the hormonal parameters

  AEP group: after 40 minutes of exercise session.

• Analysis of the "systemic metabolic milieu"_AEPInf 40

  In blood we will quantify IL-6, CRP, inflammatory cito/chemokines such as IL8, CCL2, IFN, IL10, IL1b, TNFa, TGFb that will be combined to report the inflammatory parameters

  AEP group: after 40 minutes of exercise session.

• Analysis of the "systemic metabolic milieu"_AEPLip 40

  We will analyze the Lipidomics and amino acid profiles by laboratory test that will be combined to report the composition of cell membranes

  AEP group: after 40 minutes of exercise session.

• Analysis of the "systemic metabolic milieu"_AEPcounts 40

  Whole blood cell counts will be also performed; this parameter is characterized by the absolute number as well as relative ratio.

  AEP group: after 40 minutes of exercise session.

• Analysis of the "systemic metabolic milieu"_AEPMet 80

  In plasma we will quantify pH, Lactate, Ketone bodies, Free Fatty Acids, Glucose and Insulin serum levels that will be combined to report the metabolic parameters

  AEP group: after 80 minutes of exercise session.

• Analysis of the "systemic metabolic milieu"_AEPHor 80

  In serum we will quantify ACTH, cortisol, epinephrine and norepinephrine concentrations that will be combined to report the hormonal parameters

  AEP group: after 80 minutes of exercise session.

• Analysis of the "systemic metabolic milieu"_AEPInf 80

  In blood we will quantify IL-6, CRP, inflammatory cito/chemokines such as IL8, CCL2, IFN, IL10, IL1b, TNFa, TGFb that will be combined to report the inflammatory parameters

  AEP group: after 80 minutes of exercise session.

• Analysis of the "systemic metabolic milieu"_AEPLip 80

  We will analyze the Lipidomics and amino acid profiles by laboratory test that will be combined to report the composition of cell membranes

  AEP group: after 80 minutes of exercise session.

• Analysis of the "systemic metabolic milieu"_AEPcounts 80

  Whole blood cell counts will be also performed; this parameter is characterized by the absolute number as well as relative ratio.

  AEP group: after 80 minutes of exercise session.

• Analysis of the "systemic metabolic milieu"_AEPMet 24

  In plasma we will quantify pH, Lactate, Ketone bodies, Free Fatty Acids, Glucose and Insulin serum levels that will be combined to report the metabolic parameters

  AEP group: at 24 post-exercise.

• Analysis of the "systemic metabolic milieu"_AEPHor 24

  In serum we will quantify ACTH, cortisol, epinephrine and norepinephrine concentrations that will be combined to report the hormonal parameters

  AEP group: at 24 post-exercise.

• Analysis of the "systemic metabolic milieu"_AEPInf 24

  In blood we will quantify IL-6, CRP, inflammatory cito/chemokines such as IL8, CCL2, IFN, IL10, IL1b, TNFa, TGFb that will be combined to report the inflammatory parameters

  AEP group: at 24 post-exercise.

• Analysis of the "systemic metabolic milieu"_AEPLip 24

  We will analyze the Lipidomics and amino acid profiles by laboratory test that will be combined to report the composition of cell membranes

  AEP group: at 24 post-exercise.

• Analysis of the "systemic metabolic milieu"_AEPcounts 24

  Whole blood cell counts will be also performed; this parameter is characterized by the absolute number as well as relative ratio.

  AEP group: at 24 post-exercise.

• Analysis of the "systemic metabolic milieu"_AEPMet 72

  In plasma we will quantify pH, Lactate, Ketone bodies, Free Fatty Acids, Glucose and Insulin serum levels that will be combined to report the metabolic parameters

  AEP group: at 72 hours post-exercise.

• Analysis of the "systemic metabolic milieu"_AEPHor 72

  In serum we will quantify ACTH, cortisol, epinephrine and norepinephrine concentrations that will be combined to report the hormonal parameters

  AEP group: at 72 hours post-exercise.

• Analysis of the "systemic metabolic milieu"_AEPInf 72

  In blood we will quantify IL-6, CRP, inflammatory cito/chemokines such as IL8, CCL2, IFN, IL10, IL1b, TNFa, TGFb that will be combined to report the inflammatory parameters

  AEP group: at 72 hours post-exercise.

• Analysis of the "systemic metabolic milieu"_AEPLip 72

  We will analyze the Lipidomics and amino acid profiles by laboratory test that will be combined to report the composition of cell membranes

  AEP group: at 72 hours post-exercise.

• Analysis of the "systemic metabolic milieu"_AEPcounts 72

  Whole blood cell counts will be also performed; this parameter is characterized by the absolute number as well as relative ratio.

  AEP group: at 72 hours post-exercise.

• Analysis of the "systemic metabolic milieu"_CEPMet before

  In plasma we will quantify pH, Lactate, Ketone bodies, Free Fatty Acids, Glucose and Insulin serum levels that will be combined to report the metabolic parameters

  CEP group: before exercise program.

• Analysis of the "systemic metabolic milieu"_CEPHor before

  In serum we will quantify ACTH, cortisol, epinephrine and norepinephrine concentrations that will be combined to report the hormonal parameters

  CEP group: before exercise program.

• Analysis of the "systemic metabolic milieu"_CEPInf before

  In blood we will quantify IL-6, CRP, inflammatory cito/chemokines such as IL8, CCL2, IFN, IL10, IL1b, TNFa, TGFb that will be combined to report the inflammatory parameters

  CEP group: before exercise program.

• Analysis of the "systemic metabolic milieu"_CEPLip before

  We will analyze the Lipidomics and amino acid profiles by laboratory test that will be combined to report the composition of cell membranes

  CEP group: before exercise program.

• Analysis of the "systemic metabolic milieu"_CEP counts before

  Whole blood cell counts will be also performed; this parameter is characterized by the absolute number as well as relative ratio.

  CEP group: before exercise program.

• Analysis of the "systemic metabolic milieu"_CEPMet 1w

  In plasma we will quantify pH, Lactate, Ketone bodies, Free Fatty Acids, Glucose and Insulin serum levels that will be combined to report the metabolic parameters

  CEP group: after one week of exercise program.

• Analysis of the "systemic metabolic milieu"_CEPHor 1w

  In serum we will quantify ACTH, cortisol, epinephrine and norepinephrine concentrations that will be combined to report the hormonal parameters

  CEP group: after one week of exercise program.

• Analysis of the "systemic metabolic milieu"_CEPInf 1w

  In blood we will quantify IL-6, CRP, inflammatory cito/chemokines such as IL8, CCL2, IFN, IL10, IL1b, TNFa, TGFb that will be combined to report the inflammatory parameters

  CEP group: after one week of exercise program.

• Analysis of the "systemic metabolic milieu"_CEPLip 1w

  We will analyze the Lipidomics and amino acid profiles by laboratory test that will be combined to report the composition of cell membranes

  CEP group: after one week of exercise program.

• Analysis of the "systemic metabolic milieu"_CEPcounts 1w

  Whole blood cell counts will be also performed; this parameter is characterized by the absolute number as well as relative ratio.

  CEP group: after one week of exercise program.

• Analysis of the "systemic metabolic milieu"_CEPMet 2w

  In plasma we will quantify pH, Lactate, Ketone bodies, Free Fatty Acids, Glucose and Insulin serum levels that will be combined to report the metabolic parameters

  CEP group: up to two week of exercise program.

• Analysis of the "systemic metabolic milieu"_CEPHor 2w

  In serum we will quantify ACTH, cortisol, epinephrine and norepinephrine concentrations that will be combined to report the hormonal parameters

  CEP group: up to two week of exercise program.

• Analysis of the "systemic metabolic milieu"_CEPInf 2w

  In blood we will quantify IL-6, CRP, inflammatory cito/chemokines such as IL8, CCL2, IFN, IL10, IL1b, TNFa, TGFb that will be combined to report the inflammatory parameters

  CEP group: up to two week of exercise program.

• Analysis of the "systemic metabolic milieu"_CEPLip 2w

  We will analyze the Lipidomics and amino acid profiles by laboratory test that will be combined to report the composition of cell membranes

  CEP group: up to two week of exercise program.

• Analysis of the "systemic metabolic milieu"_CEPcounts 2w

  Whole blood cell counts will be also performed; this parameter is characterized by the absolute number as well as relative ratio.

  CEP group: up to two week of exercise program.

• Analysis of the metabolic parameters by capillary sampling_AEPCap before

  Capillary sampling (prick sampling) to analysis metabolic parameters at systemic blood level will be performed during the first, in-hospital, training session and further will be continued at home, self-managed by the patient who will have to measure glycaemia and ketones every morning (finger prick sampling) and after each training sessions (earlobe prick sampling).

  AEP group: before exercise session.

• Analysis of the metabolic parameters by capillary sampling_AEPCap 40

  Capillary sampling (prick sampling) to analysis metabolic parameters at systemic blood level will be performed during the first, in-hospital, training session and further will be continued at home, self-managed by the patient who will have to measure glycaemia and ketones every morning (finger prick sampling) and after each training sessions (earlobe prick sampling).

  AEP group: after 40 minutes of exercise session.

• Analysis of the metabolic parameters by capillary sampling_AEPCap 80

  Capillary sampling (prick sampling) to analysis metabolic parameters at systemic blood level will be performed during the first, in-hospital, training session and further will be continued at home, self-managed by the patient who will have to measure glycaemia and ketones every morning (finger prick sampling) and after each training sessions (earlobe prick sampling).

  AEP group: after 80 minutes of exercise session.

• Analysis of the metabolic parameters by capillary sampling_AEPCap 24

  Capillary sampling (prick sampling) to analysis metabolic parameters at systemic blood level will be performed during the first, in-hospital, training session and further will be continued at home, self-managed by the patient who will have to measure glycaemia and ketones every morning (finger prick sampling) and after each training sessions (earlobe prick sampling).

  AEP group: at 24 post-exercise.

• Analysis of the metabolic parameters by capillary sampling_AEPCap 72

  Capillary sampling (prick sampling) to analysis metabolic parameters at systemic blood level will be performed during the first, in-hospital, training session and further will be continued at home, self-managed by the patient who will have to measure glycaemia and ketones every morning (finger prick sampling) and after each training sessions (earlobe prick sampling).

  AEP group: at 72 hours post-exercise.

• Analysis of the metabolic parameters by capillary sampling_CEPCap before

  Capillary sampling (prick sampling) to analysis metabolic parameters at systemic blood level will be performed during the first, in-hospital, training session and further will be continued at home, self-managed by the patient who will have to measure glycaemia and ketones every morning (finger prick sampling) and after each training sessions (earlobe prick sampling).

  CEP group: during the first training session

• Analysis of the metabolic parameters by capillary sampling_CEPCap 2w

  Capillary sampling (prick sampling) to analysis metabolic parameters at systemic blood level will be performed during the first, in-hospital, training session and further will be continued at home, self-managed by the patient who will have to measure glycaemia and ketones every morning (finger prick sampling) and after each training sessions (earlobe prick sampling).

  CEP group: every morning up to two weeks.

• Analysis of the metabolic parameters by capillary sampling_CEPCap end

  Capillary sampling (prick sampling) to analysis metabolic parameters at systemic blood level will be performed during the first, in-hospital, training session and further will be continued at home, self-managed by the patient who will have to measure glycaemia and ketones every morning (finger prick sampling) and after each training sessions (earlobe prick sampling).

  CEP group: at the end of training sessions up to two weeks.

Other Outcomes (2)

• Physical Activity Questionnaire

  Within one month of the enrollment

• MeDiet questionnaire

  Within one month of the enrollment

Study Arms (2)

AEP Group

EXPERIMENTAL

First series of patients (10 pts) will be assigned to the Acute Exercise Protocol Group (AEP Group). The acute program consists in a single walking session on a treadmill lasting 80 minutes. The exercise session will begin with a 10-minute warm-up at the patient's self selected comfortable speed. On the ending of warm up, treadmill speed will be increased until reaching target HRR zone. Then the treadmill speed will be maintained stable throughout the exercise session. Cardiac workload will be monitored by a Sport-watch (Garmin Forerunner) and the walking biomechanics by a foot sensor (Garmin Running Dynamic Pod Sensore).

Other: AEP Group Walking Sessions

CEP Group

EXPERIMENTAL

Second series of patients (10 pts) will be assigned to the Chronic Exercise Protocol Group (CEP Group). The chronic program consists in a walking session on a treadmill lasting 80 minutes (depending on the AEP results), repeated three time a week for three weeks. The walking intensity will be defined during a treadmill test performedbefore the beginning of the exercise program. Each exercise session will beginwith a 10-minute warm-up at the patient's self selected comfortable speed. On the ending of warm up, patients will increase treadmill speed until reaching target HRR zone.Then the treadmill speed will be maintained stable throughout the exercise session. The first training session will be organized in hospital with supervision of research staff. Cardiac workload will be monitored by a Sport-watch (Garmin Forerunner) and walking biomechanics by a foot sensor (Garmin Running Dynamic Pod Sensore).

Other: CEP Group Walking Sessions

Interventions

AEP Group Walking Sessions OTHER

The AEP Program consists in a single walking session on a treadmill lasting 80 minutes

AEP Group

CEP Group Walking Sessions OTHER

The chronic program consists in a walking session on a treadmill lasting 80 minutes (depending on the AEP results), repeated three time a week for three weeks.

CEP Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age from 18 to 65 years at the time of recruitment
• Histologically confirmed diagnosis of primary melanoma
• Patients who are candidate to curative surgery for primary melanoma, skin radicalization or sentinel node biopsy.
• American Society of Anaesthesiologists (ASA) status I
• Willingness and ability to comply with the protocol, the scheduled visits, treatment plans, laboratory tests and other procedures.
• Understanding and signature of the informed consent
• Female patients of childbearing potential must agree to sexual abstinence or to use highly effective method of contraception throughout the study (for CEP patients)

You may not qualify if:

• American Society of Anaesthesiologists (ASA) status \> I
• Pregnancy or lactation
• Known infection from HIV virus
• Regular physical exercise (more than 1 exercise workout of moderate to intense exercise activity per week)
• Any physical or mental conditions interfering with the ability to perform exercise or to complete the testing procedures.

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy, 20033, Italy

Location

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MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Licia Rivoltini, MD

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Pre/post intervention, two-arms, sequential study. Patients with newly diagnose of melanoma are eligible.The study will enroll a total of 20 patients (10 in the AEP and 10 in the CEP), who will be enrolled approximately in 12-13 months.The first series of patients will be assigned to the Acute Exercise Program (AEP group), the second series to the Chronic Exercise Program (CEP group). The final endpoint is to verify whether short-term physical exercise can represent a feasible and safe tool for re-setting antitumor immunity in early melanoma patients. Investigators will analyze how the acute physical exercise modifies systemic immunity and biochemical/metabolic parameters. Specifically, Investigators will verify whether the exercise will modify:1 the immunological profiling of blood including frequency and function of MDSC, together with the concomitant status of antitumor immunity; 2 blood concentration of biochemical and metabolic parameters related to physical exercise and immunity

Study Record Dates

• First Submitted: April 29, 2021
• First Posted: November 14, 2022
• Study Start: January 20, 2020
• Primary Completion: November 30, 2023
• Study Completion: December 31, 2023
• Last Updated: October 15, 2024

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)