Define the role of immune response on radiation therapy outcomes in patients with HPV-associated gynecologic cancers. A currently ongoing trial is evaluating serial changes in the immune response during radiation therapy in patients with cervical cancer treated with standard of care approach or HPV direct vaccine coupled with chemoradiation. Small volume samples are used for multi-spectral flow cytometry, T-cell receptor sequencing, whole exome sequencing and function expansion assays to characterize the impact of radiation on immune activation.
- Expansion of Candidate HPV-Specific T Cells in the Tumor Microenvironment during Chemoradiotherapy Is Prognostic in HPV16+ Cancers
Colbert LE, El MB, Lynn EJ, Bronk J, Karpinets TV, Wu X, Chapman BV, Sims TT, Lin D, Kouzy R, Sammouri J, Biegert G, Delgado Medrano AY, Olvera A, Sastry KJ, Eifel PJ, Jhingran A, Lin L, Ramondetta LM, Futreal AP, Jazaeri AA, Schmeler KM, Yue J, Mitra A, Yoshida-Court K, Wargo JA, Solley TN, Hegde V, Nookala SS, Yanamandra AV, Dorta-Estremera S, Mathew G, Kavukuntla R, Papso C, Ahmed-Kaddar M, Kim M, Zhang J, Reuben A, Holliday EB, Minsky BD, Koong AC, Koay EJ, Das P, Taniguchi CM, Klopp A. Cancer Immunol Res. 2022 Feb;10(2):259-271. doi: 10.1158/2326-6066.CIR-21-0119. Epub 2022 Jan 19. PMID: 35045973
- Kinetics of Intratumoral Immune Cell Activation During Chemoradiation for Cervical Cancer Dorta-Estremera Colbert LE, Nookala SS, Yanamandra AV, Yang G, Delgado A, Mikkelson M, Eifel P, Jhingran A, Lilie LL, Welsh J, Schmeler K, Sastry JK 1, Klopp A. Int J Radiat Oncol Biol Phys. 2018 Nov 1;102(3):593-600. PMCID: PMC6721616
We have identified microbiome signatures associated with toxicity and survival in patients with HPV cancers. Investigations into how to manipulate the microbiome to improve outcomes are under development.
- Gut microbiome diversity is an independent predictor of survival in cervical cancer patients receiving chemoradiation. Sims TT, El Alam MB, Karpinets TV, Dorta-Estremera S, Hegde VL, Nookala S, Yoshida-Court K, Wu X, Biegert GWG, Delgado Medrano AY, Solley T, Ahmed-Kaddar M, Chapman BV, Sastry KJ, Mezzari MP, Petrosino JF, Lin LL, Ramondetta L, Jhingran A, Schmeler KM, Ajami NJ, Wargo J, Colbert LE, Klopp AH. Commun Biol. 2021 Feb 22;4(1):237. doi: 10.1038/s42003-021-01741- x.PMID: 33619320
- Microbial Diversity and Composition is Associated with Patient Reported Toxicity during Chemoradiation. Mitra A, Grossman Biegart GW, Delgado AY, Karpinets T, Solley TN, Mezzari MP, Yoshida-Court K, Petrosino JF, Mikkelson MD, Lin L, Eifel P, Zhang J, Ramondetta LM, Jhingran AJ, Sims TT, Schmeler K, Okhuysen, P, Colbert LE and Klopp AH. Int J Radiat Oncol Biol Phys 2020 May 1;107(1):163- 171. PMID: 31987960
- Gut microbial diversity and genus-level differences identified in cervical cancer patients versus healthy controls. Sims TT, Colbert LE, Zheng J, Delgado Medrano AY, Hoffman KL, Ramondetta L, Jazaeri A, Jhingran A, Schmeler KM, Daniel CR, Klopp A. Gynecol Oncol 2019 Nov;155(2):237-244. PMID: 31500892
- Gut microbiome diversity is an independent predictor of survival in cervical cancer patients receiving chemoradiation. Sims TT, El Alam MB, Karpinets TV, Dorta-Estremera S, Hegde VL, Nookala S, Yoshida-Court K, Wu X, Biegert GWG, Delgado Medrano AY, Solley T, Ahmed-Kaddar M, Chapman BV, Sastry KJ, Mezzari MP, Petrosino JF, Lin LL, Ramondetta L, Jhingran A, Schmeler KM, Ajami NJ, Wargo J, Colbert LE, Klopp AH. Commun Biol. 2021 Feb 22;4(1):237. doi: 10.1038/s42003-021-01741-x. PMID: 33619320; PMCID: PMC7900251
Determining the role of MRI guidance in brachytherapy for cervical cancer. We have developed clinical trials aimed at optimizing brachytherapy for cervical cancer, progressing from comparison with CT to MRI to incorporating active MRI guidance into gynecologic brachytherapy using hybrid applicators.
- Developing an intraoperative eT MRI guided brachytherapy program within a diagnostic imaging suite. Ning MS, Venkatesan AM, Stafford RJ, Bui TP, Carlson R 3rd, Bailard NS, Vedam S, Davis R, Olivieri ND, Guzman AB, Incalcaterra JR, McKelvey FA, Thaker NG, Rauch GM, Tang C, Frank SJ, Joyner MM, Lin LL, Jhingran A, Eifel PJ, Klopp AH. Brachytherapy 2019. Jul-Aug 2020;19(4):427-437. PMID: 31786169
- Clinical Utility of a MRI positive line marper in image guided brachytherapy for gynecologic malignancies. Ning MS, Vedam S, Ma J, Stafford RJ, Bruno TL, Cunningham M, Starks C, Lawyer A, Venkatesan AM, Wang L, Wang J, Olivieri ND, Guzman AB, Incalcaterra JR, Thaker NG, Joyner MM, Lin LL, Jhingran A, Eifel PJ, Klopp AH. Brachytherapy 2020. PMID: 32265119
- Pilot study of a computed tomography-compatible shielded intracavitary brachytherapy applicator for treatment of cervical cancer. Klopp AH, Mourtada F, Yu ZH, Beadle BM, Munsell MF, Jhingran A, Eifel PJ. Pract Radiat Oncol Apr-Jun 2013;3(2):115-23. PMID: 24674314
- Optimizing packing contrast for MRI-based intracavitary brachytherapy planning for cervical cancer. Swanick CW, Castle KO, Rechner LA, Rauch GM, Jhingran A, Eifel PJ, Klopp AH. Brachytherapy May-Jun 2015;14(3):385-9. PMID: 25620163
Refine the role of radiation therapy for gynecologic cancers including treatment of oligometastatic cancers. We have reported on our own experience with definitive RT to metastatic disease leading to long term survival. I led the phase III randomized trial RTOG 1203/TIME-C demonstrated that IMRT reduced patient reported toxicity. We found that bone marrow dose is predictive of hematologic toxicity from bone marrow radiation. We reported on the outcomes of patients treated with paraaortic IMRT, which led to the recognition of duodenal toxicity in these patients. In subsequent analyses, we identified a dosimetric parameter predictive of duodenal toxicity.
- Patient-Reported Toxicity During Pelvic Intensity-Modulated Radiation Therapy: NRG Oncology-RTOG 1203. Klopp AH, Yeung AR, Deshmukh S, Gil KM, Wenzel L, Westin SN, Gifford K, Gaffney DK, Small Jr W, Thompson S, Doncals DE, Cantuaria GHC, Yaremko BP, Chang A, Kundapur V, Mohan DS, Haas ML, Kim YB, Ferguson CL, Pugh SL, Kachnic LA, Bruner DW. J Clin Oncol. 2018 Aug 20;36(24):2538-2544. PMID: 29989857
- Outcomes and patterns of relapse after definitive radiation therapy for oligometastatic cervical cancer. Ning MS, Ahobila V, Jhingran A, Stecklein SR, Frumovitz M, Schmeler KM, Eifel PJ, Klopp AH. Gynecol Oncol. 2018 Jan;148(1):132-138. doi: 10.1016/j.ygyno.2017.10.017. Epub 2017 Oct 28. PMID: 29089122.
- Improvement in Patient-Reported Outcomes With Intensity-Modulated Radiotherapy (RT) Compared With Standard RT: A Report From the NRG Oncology RTOG 1203 Study. Yeung AR, Pugh SL, Klopp AH, Gil KM, Wenzel L, Westin SN, Gaffney DK, Small W Jr, Thompson S, Doncals DE, Cantuaria GHC, Yaremko BP, Chang A, Kundapur V, Mohan DS, Haas ML, Kim YB, Ferguson CL, Deshmukh S, Bruner DW, Kachnic LA. J Clin Oncol. 2020 May 20;38(15):1685-1692. doi: 10.1200/JCO.19.02381. Epub 2020 Feb 19. PMID: 32073955; PMCID: PMC7238486.
- Dosimetric Predictors of Duodenal Toxicity After Intensity Modulated Radiation Therapy for Treatment of the Para-aortic Nodes in Gynecologic Cancer. Verma J, Sulman EP, Jhingran A, Tucker SL, Rauch GM, Eifel PJ, Klopp AH. Int J Radiat Oncol Biol Phys. 2014 Feb 1;88(2):357- 62. PMID: 24411609
We found that adipose-derived stromal cells from visceral and omental adipose have a unique phenotype and mediate the tumor promoting effects of adipose on cancer. adipose-derived stromal cells promote the migration and chemoresistance of ovarian cancers. We were the first group to characterize adipose-derived stromal cells from the visceral adipose. We found that omental adipose-derived stromal cells more potently promoted tumor growth than subcutaneous or bone marrow-derived stromal cells in a murine endometrial cancer model. We determined that obesity changes the phenotype of adipose-derived stromal cells, identifying a novel mechanism by which obesity supports growth of ovarian cancers.
- Omental adipose tissue-derived stromal cells promote vascularization and growth of endometrial tumors. Klopp AH, Zhang Y, Solley T, Amaya-Manzanares F, Marini F, Andreeff M, Debeb B, Woodward W, Schmandt R, Broaddus R, Lu K, Kolonin MG. Clin Cancer Res. 2012 Feb 1;18(3):771-82. PMCID: PMC3481843
- Human omental- derived adipose stem cells increase ovarian cancer proliferation, migration and chemoresistance. Nowicka A, Marini FC, Solley TN, Elizondo PB, Zhang Y, Sharp HJ, Broaddus R, Kolonin M, Mok SC, Thompson MS, Woodward WA, Lu K, Salimian B, Nagrath D, Klopp AH. PLoS One. 2013 Dec 2;8(12):e81859. PMCID: PMC3847080
- Stromal Cells Derived from Visceral and Obese Adipose Tissue Promote Growth of Ovarian Cancers. Zhang Y, Nowicka A, Solley TN, Wei C, Parikh A, Court L, Burks JK, Andreeff M, Woodward WA, Dadbin A, Kolonin MG, Lu KH, Klopp AH. PLoS One. 2015 Aug 28;10(8):e0136361. PMID: 26317219
- Extracellular vesicles derived from ascitic fluid enhance growth and migration of ovarian cancer cells. Mitra A, Yoshida-Court K, Solley TN, Mikkelson M, Yeung CLA, Nick A, Lu K, Klopp AH. Sci Rep. 2021 Apr 28;11(1):9149. doi: 10.1038/s41598-021-88163-1. PMID: 33911091; PMCID: PMC8080718.