About Kathleen M. Kokolus
I received my PhD in Tumor Immunology from SUNY Buffalo while working under Elizabeth Repasky, PhD. Our work showed that adrenergic stress in murine cancer models both impaired the CD8+ T cell mediated anti-tumor immune response and increased immunosuppressive factors- both negative indicators for cancer survival. We discovered that reducing stress by housing tumor-bearing mice at their thermoneutral temperature restored immunity resulting in improved survival and an immunostimulatory tumor microenvironment.
During my postdoctoral fellowship with Todd Schell, PhD (Penn State College of Medicine) I recognized the inconsistency in immunotherapy response among cancer patients. Immunotherapy targets a patient’s own immune system and can produce long-term, durable responses in patients with advanced cancers; however, only about 20% of patients benefit from this robust response. Building upon my previous work, we investigated therapeutic options to relieve adrenergic stress in the effort to improve immunotherapeutic efficacy. We demonstrated, for the first time, that patients with advanced melanoma who were taking β-adrenergic antagonists (ie β-blockers), which block adrenergic signaling, have significantly better response to and survival following immunotherapy.
I returned to Roswell Park in 2018 to work with Pawel Kalinski, MD, PhD. We are developing therapeutic options that further enhance the efficacy of immunotherapies by counteracting prostaglandin E2 (PGE2), a biologic factor which reduces anti-tumor immune activity by suppressing CD8+ T cell-mediated responses and hindering dendritic cell recruitment of T cells.
My broad research interests include immunology, stress and oncology. I am focused on studying immunotherapy, one of the most promising treatments available for patients with advanced cancers. As only small proportions of patients experience durable, complete responses from these therapies, increasing responders is a major interest I concentrate on in my current research. It has become evident that gaining a firm understanding of how stress impacts the immune response and the efficacy of immunotherapy is vital to achieve the most benefit from these cancer treatments. Although the interplay between the stress and immune systems has been long recognized, the precise mechanisms by which these systems affect one another are not well understood, particularly in the immunotherapy setting. Developing a strong and robust understanding of the complex interactions between these two systems has the potential to guide us towards novel treatments to significantly broaden the base of patients who benefit from immunotherapy.
In addition to my research, I am highly motivated to do my part in training the next generation of cancer researchers. I teach classes for the Roswell Park Graduate program each semester and I am the course director of Techniques and Analyses for Cancer Sciences (RPG599). I am also always open to mentoring students and interns in the lab.
Working at a comprehensive cancer center gives me the privilege of collaborating with teams of physicians and scientists focused on developing novel treatments that will directly impact patient survivorship. I am grateful for the opportunity to advance my research in a highly collaborate and scientifically motivated cancer center like Roswell Park.
Roswell Park Comprehensive Cancer Center
- Research Assistant Professor of Oncology
- Department of Immunology
State University of New York at Buffalo
- Associate Member, Tumor Immunology and Immunotherapy
- Roswell Park Graduate Division
Education and Training:
- 2007- BS - Biology, Duquesne University, Pittsburgh, PA
- 2008- MS - Forensic Science and Law, Duquesne University, Pittsburgh, PA
- 2014 - PhD - Tumor Immunology, State University of New York at Buffalo, Roswell Park Graduate Division, Buffalo, NY
- Penn State College of Medicine, Hershey, PA
- American Association for Cancer Research (AACR)
- Society for Immunotherapy of Cancer (SITC)
- Translational Research Cancer Center Consortium (TRCCC)
- American Association of Immunologists (AAI)
Cancer immunotherapies have emerged as a leading therapeutic option for many patients with late stage and hard to treat cancers. The advent of these groundbreaking therapies has presented treatment options to patients who have not responded to more traditional treatment regimens. Seeing how immunotherapies can extend the lives of patients who otherwise have no viable treatment options has solidified my focus on immunotherapy research. While many patients benefit from long-lasting immunity following immunotherapy treatment, there are still a large percentage of patients who do not respond to these therapies.
I am working to contribute to the immunotherapy field and my research interests are focused on three major goals:
1) Improving the efficacy of immune checkpoint inhibitors
2) Expanding the immunotherapy-responsive patient population
3) Reducing toxicities associated with immunotherapy use to improve quality of life in cancer survivors
1) Schweinfurthin natural products induce regression of murine melanoma and pair with anti-PD-1 therapy to facilitate durable tumor immunity. Kokolus KM, Haley JS, Koubek EJ, Gowda R, Dinavahi SS, Sharma A, Claxton DF, Helm KF, Drabick JJ, Robertson GP, Neighbors JD, Hohl RJ, Schell TD. Oncoimmunology. 2018 Nov 11;8(2):e1539614. doi: 10.1080/2162402X.2018.1539614. eCollection 2019. PMID: 30713799
2) Beta blocker use correlates with better overall survival in metastatic melanoma patients and improves the efficacy of immunotherapies in mice. Kokolus KM, Zhang Y, Sivik JM, Schmeck C, Zhu J, Repasky EA, Drabick JJ, Schell TD. Oncoimmunology. 2017 Dec 21;7(3):e1405205. doi: 10.1080/2162402X.2017.1405205. eCollection 2018. PMID: 29399407
3) β-Adrenergic Signaling in Mice Housed at Standard Temperatures Suppresses an Effector Phenotype in CD8+ T Cells and Undermines Checkpoint Inhibitor Therapy. Bucsek MJ, Qiao G, MacDonald CR, Giridharan T, Evans L, Niedzwecki B, Liu H, Kokolus KM, Eng JW, Messmer MN, Attwood K, Abrams SI, Hylander BL, Repasky EA. Cancer Res. 2017 Oct 15;77(20):5639-5651. doi: 10.1158/0008-5472.CAN-17-0546. Epub 2017 Aug 17. PMID: 28819022
4) Housing temperature-induced stress drives therapeutic resistance in murine tumour models through β2-adrenergic receptor activation. Eng JW, Reed CB, Kokolus KM, Pitoniak R, Utley A, Bucsek MJ, Ma WW, Repasky EA, Hylander BL. Nat Commun. 2015 Mar 10;6:6426. doi: 10.1038/ncomms7426. PMID: 25756236
5) Baseline tumor growth and immune control in laboratory mice are significantly influenced by subthermoneutral housing temperature. Kokolus KM, Capitano ML, Lee CT, Eng JW, Waight JD, Hylander BL, Sexton S, Hong CC, Gordon CJ, Abrams SI, Repasky EA. Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20176-81. doi: 10.1073/pnas.1304291110. Epub 2013 Nov 18. PMID: 24248371