Circulating neutrophils and tumor-associated myeloid cells function as a powerful biomarker for response to chemoradiation in locally advanced cervical cancer
Purpose: The immune system’s role in mediating the cytotoxic effects of chemoradiotherapy remains not completely understood. The integration of immunotherapies into treatment will require insight into features and timing of the immune microenvironment associated with treatment response. Here, we inv...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-03-01
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| Series: | Clinical and Translational Radiation Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405630823000034 |
| _version_ | 1811162738108399616 |
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| author | Olsi Gjyshi Adam Grippin Lauren Andring Anuja Jhingran Lilie L. Lin Julianna Bronk Patricia J. Eifel Melissa M. Joyner Jagannadha K. Sastry Kyoko Yoshida-Court Travis N. Solley Tatiana Cisneros Napravnik Madison P. O'Hara Venkatesh L Hegde Lauren E. Colbert Ann H Klopp |
| author_facet | Olsi Gjyshi Adam Grippin Lauren Andring Anuja Jhingran Lilie L. Lin Julianna Bronk Patricia J. Eifel Melissa M. Joyner Jagannadha K. Sastry Kyoko Yoshida-Court Travis N. Solley Tatiana Cisneros Napravnik Madison P. O'Hara Venkatesh L Hegde Lauren E. Colbert Ann H Klopp |
| author_sort | Olsi Gjyshi |
| collection | DOAJ |
| description | Purpose: The immune system’s role in mediating the cytotoxic effects of chemoradiotherapy remains not completely understood. The integration of immunotherapies into treatment will require insight into features and timing of the immune microenvironment associated with treatment response. Here, we investigated the role of circulating neutrophils and tumor-associated myeloid cells (TSAMs) as potential agents and biomarkers for disease-related outcomes in locally advanced cervical cancer (LACC). Material and Methods: Hematologic parameters for two LACC patient cohorts, a retrospective clinical and a prospective translational cohort, were obtained at baseline, weekly during chemoradiotherapy for the retrospective cohort, biweekly during chemoradiotherapy for the prospective cohort, and at the first follow-up visit for both cohorts (mean 14.7 weeks, range 8.1–25.1 weeks for the prospective cohort and 5.3 weeks with a range of 2.7–9.0 weeks for the retrospective cohort). In both cohorts, baseline as well as mean and lowest on-treatment values for platelets, hemoglobin, absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) were analyzed for correlations with disease-related outcomes. In the prospective cohort, circulating myeloid cells were isolated from peripheral blood mononuclear cells (PBMCs), and TSAMs were isolated from tumor tissue via a novel serial cytobrush sampling assay. The samples were analyzed by flow cytometry. Results: In both cohorts, the only hematologic parameter significantly associated with survival was elevated on-treatment mean ANC (mANC), which was associated with lower local failure-free and overall survival rates in the retrospective and prospective cohorts, respectively. mANC was not associated with a difference in distant metastases. CD11b+CD11c- TSAMs, which act as a surrogate marker for intratumoral neutrophils, steadily decreased during the course of chemoRT and nadier’d at week 5 of treatment. Conversely, circulating myeloid cells identified from PBMCs steadily increased through week 5 of treatment. Regression analysis confirmed an inverse relationship between circulating myeloid cells and TSAMs at this time point. Conclusions: These findings identify on-treatment mean neutrophil count as a predictor of disease-related outcomes, suggest that neutrophils contribute to chemoradiation treatment resistance, and demonstrate the importance of techniques to measure intratumoral immune activity. |
| first_indexed | 2024-04-10T06:34:07Z |
| format | Article |
| id | doaj.art-7f3ed66fbc544424af486805649d57a8 |
| institution | Directory Open Access Journal |
| issn | 2405-6308 |
| language | English |
| last_indexed | 2024-04-10T06:34:07Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Clinical and Translational Radiation Oncology |
| spelling | doaj.art-7f3ed66fbc544424af486805649d57a82023-03-01T04:32:19ZengElsevierClinical and Translational Radiation Oncology2405-63082023-03-0139100578Circulating neutrophils and tumor-associated myeloid cells function as a powerful biomarker for response to chemoradiation in locally advanced cervical cancerOlsi Gjyshi0Adam Grippin1Lauren Andring2Anuja Jhingran3Lilie L. Lin4Julianna Bronk5Patricia J. Eifel6Melissa M. Joyner7Jagannadha K. Sastry8Kyoko Yoshida-Court9Travis N. Solley10Tatiana Cisneros Napravnik11Madison P. O'Hara12Venkatesh L Hegde13Lauren E. Colbert14Ann H Klopp15Department of Radiation Oncology, Saint Elizabeth Cancer Center, Edgewood, KY, United StatesDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Department of Medicine, United StatesDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Department of Medicine, United StatesDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Department of Medicine, United StatesDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Department of Medicine, United StatesDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Department of Medicine, United StatesDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Department of Medicine, United StatesDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Department of Medicine, United StatesDepartment of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Department of Medicine, United StatesDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Department of Medicine, United StatesDepartment of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Department of Medicine, United States; Corresponding authors at: Department of Radiation Oncology, Unit 1052, The University of Texas MD Anderson Cancer Center, 6565 MD Anderson Blvd., Houston, TX, 77030, United States, (L.E. Colbert); Department of Radiation Oncology, Unit 1422, The University of Texas MD Anderson Cancer Center, 1400 Pressler St., Houston, TX, 7703, United States, (A.H. Klopp).Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Department of Medicine, United States; Corresponding authors at: Department of Radiation Oncology, Unit 1052, The University of Texas MD Anderson Cancer Center, 6565 MD Anderson Blvd., Houston, TX, 77030, United States, (L.E. Colbert); Department of Radiation Oncology, Unit 1422, The University of Texas MD Anderson Cancer Center, 1400 Pressler St., Houston, TX, 7703, United States, (A.H. Klopp).Purpose: The immune system’s role in mediating the cytotoxic effects of chemoradiotherapy remains not completely understood. The integration of immunotherapies into treatment will require insight into features and timing of the immune microenvironment associated with treatment response. Here, we investigated the role of circulating neutrophils and tumor-associated myeloid cells (TSAMs) as potential agents and biomarkers for disease-related outcomes in locally advanced cervical cancer (LACC). Material and Methods: Hematologic parameters for two LACC patient cohorts, a retrospective clinical and a prospective translational cohort, were obtained at baseline, weekly during chemoradiotherapy for the retrospective cohort, biweekly during chemoradiotherapy for the prospective cohort, and at the first follow-up visit for both cohorts (mean 14.7 weeks, range 8.1–25.1 weeks for the prospective cohort and 5.3 weeks with a range of 2.7–9.0 weeks for the retrospective cohort). In both cohorts, baseline as well as mean and lowest on-treatment values for platelets, hemoglobin, absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) were analyzed for correlations with disease-related outcomes. In the prospective cohort, circulating myeloid cells were isolated from peripheral blood mononuclear cells (PBMCs), and TSAMs were isolated from tumor tissue via a novel serial cytobrush sampling assay. The samples were analyzed by flow cytometry. Results: In both cohorts, the only hematologic parameter significantly associated with survival was elevated on-treatment mean ANC (mANC), which was associated with lower local failure-free and overall survival rates in the retrospective and prospective cohorts, respectively. mANC was not associated with a difference in distant metastases. CD11b+CD11c- TSAMs, which act as a surrogate marker for intratumoral neutrophils, steadily decreased during the course of chemoRT and nadier’d at week 5 of treatment. Conversely, circulating myeloid cells identified from PBMCs steadily increased through week 5 of treatment. Regression analysis confirmed an inverse relationship between circulating myeloid cells and TSAMs at this time point. Conclusions: These findings identify on-treatment mean neutrophil count as a predictor of disease-related outcomes, suggest that neutrophils contribute to chemoradiation treatment resistance, and demonstrate the importance of techniques to measure intratumoral immune activity.http://www.sciencedirect.com/science/article/pii/S2405630823000034NeutrophilsBiomarkerRadiation oncologyCervical cancerImmunobiology |
| spellingShingle | Olsi Gjyshi Adam Grippin Lauren Andring Anuja Jhingran Lilie L. Lin Julianna Bronk Patricia J. Eifel Melissa M. Joyner Jagannadha K. Sastry Kyoko Yoshida-Court Travis N. Solley Tatiana Cisneros Napravnik Madison P. O'Hara Venkatesh L Hegde Lauren E. Colbert Ann H Klopp Circulating neutrophils and tumor-associated myeloid cells function as a powerful biomarker for response to chemoradiation in locally advanced cervical cancer Clinical and Translational Radiation Oncology Neutrophils Biomarker Radiation oncology Cervical cancer Immunobiology |
| title | Circulating neutrophils and tumor-associated myeloid cells function as a powerful biomarker for response to chemoradiation in locally advanced cervical cancer |
| title_full | Circulating neutrophils and tumor-associated myeloid cells function as a powerful biomarker for response to chemoradiation in locally advanced cervical cancer |
| title_fullStr | Circulating neutrophils and tumor-associated myeloid cells function as a powerful biomarker for response to chemoradiation in locally advanced cervical cancer |
| title_full_unstemmed | Circulating neutrophils and tumor-associated myeloid cells function as a powerful biomarker for response to chemoradiation in locally advanced cervical cancer |
| title_short | Circulating neutrophils and tumor-associated myeloid cells function as a powerful biomarker for response to chemoradiation in locally advanced cervical cancer |
| title_sort | circulating neutrophils and tumor associated myeloid cells function as a powerful biomarker for response to chemoradiation in locally advanced cervical cancer |
| topic | Neutrophils Biomarker Radiation oncology Cervical cancer Immunobiology |
| url | http://www.sciencedirect.com/science/article/pii/S2405630823000034 |
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