Research is a cornerstone of MD Anderson’s quest to end cancer. The Excellence in Science program is the online showcase for the Wall of Science, our quarterly program for honoring outstanding primary research selected from among publications in top journals by MD Anderson’s world-renowned scientists.
2022 Quarter 2 Awardees (Dec 2021-Feb 2022)

Dr. Hortobagyi
21-gene assay to inform chemotherapy benefit in node-positive breast cancer – The New England Journal of Medicine

Drs. McQuade, Cohen, Daniel & Wargo
Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response - Science

Drs. Park & Song
NEAT1 is essential for metabolic changes that promote breast cancer growth and metastasis - Cell Metabolism

Dr. Tawbi
Relatlimab and Nivolumab versus Nivolumab in untreated advanced melanoma - The New England Journal of Medicine

Dr. Westin
Axicabtagene ciloleucel as second-line therapy for large b-cell lymphoma - The New England Journal of Medicine

Drs. Xiao & Yu
The allergy mediator histamine confers resistance to immunotherapy in cancer patients via activation of the macrophage histamine receptor H1 – Cancer Cell
September - November 2021
Gabriel N. Hortobagyi, M.D.
The New England Journal of Medicine
21-gene assay to inform chemotherapy benefit in node-positive breast cancer
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Jennifer McQuade, M.D., Lorenzo Cohen, Ph.D., Carrie Daniel-MacDougall, Ph.D., Jennifer Wargo, M.D.
Science
Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response
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Mikung Park, Ph.D. and Min Sup Song, Ph.D.
Cell Metabolism
NEAT1 is essential for metabolic changes that promote breast cancer growth and metastasis
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Hussein Tawbi, M.D., Ph.D.
The New England Journal of Medicine
Relatlimab and Nivolumab versus Nivolumab in untreated advanced melanoma
Read more
Jason Robert Westin, M.D.
The New England Journal of Medicine
Axicabtagene ciloleucel as second-line therapy for large b-cell lymphoma
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Yi Xiao, Ph.D. and Dihua Yu, M.D., Ph.D.
Cancer Cell
The allergy mediator histamine confers resistance to immunotherapy in cancer patients via activation of the macrophage histamine receptor H1
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Gabriel N. Hortobagyi, M.D.
21-gene assay to inform chemotherapy benefit in node-positive breast cancer
Background
The recurrence score based on the 21-gene breast-cancer assay has been clinically useful in predicting a chemotherapy benefit in hormone-receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative, axillary lymph-node–negative breast cancer. In women with positive lymph-node disease, the role of the recurrence score with respect to predicting a benefit of adjuvant chemotherapy is unclear.
Methods
In a prospective trial, we randomly assigned women with hormone-receptor–positive, HER2-negative breast cancer, one to three positive axillary lymph nodes, and a recurrence score of 25 or lower (scores range from 0 to 100, with higher scores indicating a worse prognosis) to endocrine therapy only or to chemotherapy plus endocrine (chemoendocrine) therapy. The primary objective was to determine the effect of chemotherapy on invasive disease–free survival and whether the effect was influenced by the recurrence score. Secondary end points included distant relapse–free survival.
Results
A total of 5083 women (33.2% premenopausal and 66.8% postmenopausal) underwent randomization, and 5018 participated in the trial. At the prespecified third interim analysis, the chemotherapy benefit with respect to increasing invasive disease–free survival differed according to menopausal status (P=0.008 for the comparison of chemotherapy benefit in premenopausal and postmenopausal participants), and separate prespecified analyses were conducted. Among postmenopausal women, invasive disease–free survival at 5 years was 91.9% in the endocrine-only group and 91.3% in the chemoendocrine group, with no chemotherapy benefit (hazard ratio for invasive disease recurrence, new primary cancer [breast cancer or another type], or death, 1.02; 95% confidence interval [CI], 0.82 to 1.26; P=0.89). Among premenopausal women, invasive disease–free survival at 5 years was 89.0% with endocrine-only therapy and 93.9% with chemoendocrine therapy (hazard ratio, 0.60; 95% CI, 0.43 to 0.83; P=0.002), with a similar increase in distant relapse–free survival (hazard ratio, 0.58; 95% CI, 0.39 to 0.87; P=0.009). The relative chemotherapy benefit did not increase as the recurrence score increased.
Conclusions
Among premenopausal women with one to three positive lymph nodes and a recurrence score of 25 or lower, those who received chemoendocrine therapy had longer invasive disease–free survival and distant relapse–free survival than those who received endocrine-only therapy, whereas postmenopausal women with similar characteristics did not benefit from adjuvant chemotherapy. (Funded by the National Cancer Institute and others; RxPONDER ClinicalTrials.gov number, NCT01272037. opens in new tab.)
Kevin Kalinsky, William E. Barlow, Julie R. Gralow, Funda Meric-Bernstam, Kathy S. Albain, Daniel F. Hayes, Nancy U. Lin, Edith A. Perez, Lori J. Goldstein, Stephen K.L. Chia, Sukhbinder Dhesy-Thind, Priya Rastogi, Emilio Alba, Suzette Delaloge, Miguel Martin, Catherine M. Kelly, Manuel Ruiz-Borrego, Miguel Gil-Gil, Claudia H. Arce-Salinas, Etienne G.C. Brain Eun Sook Lee, Jean Yves Pierga, Begoña Bermejo, Manuel Ramos-Vazquez, Kyung Hae Jung, Jean Marc Ferrero, Anne F. Schott, Steven Shak, Priyanka Sharma, Danika L. Lew, Jieling Miao, Debasish Tripathy, Lajos Pusztai, Gabriel N. Hortobagyi
Clinical Professor, Department of Breast Medical Oncology
Jennifer McQuade, M.D., Lorenzo Cohen, Ph.D., Carrie Daniel-MacDougall, Ph.D., Jennifer Wargo, M.D.
Assistant Professor, Department of Melanoma Medical Oncology
Professor, Departments of Palliative, Rehab & Integrative Medicine and Behavioral Science
Richard E. Haynes Distinguished Professorship for Clinical Cancer Prevention
Associate Professor, Department of Epidemiology
Professor, Departments of Surgical Oncology and Genomic Med Research
Doctor R Lee Clark Professorship
Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response
Gut bacteria modulate the response to immune checkpoint blockade (ICB) treatment in cancer, but the effect of diet and supplements on this interaction is not well studied. We assessed fecal microbiota profiles, dietary habits, and commercially available probiotic supplement use in melanoma patients and performed parallel preclinical studies. Higher dietary fiber was associated with significantly improved progression-free survival in 128 patients on ICB, with the most pronounced benefit observed in patients with sufficient dietary fiber intake and no probiotic use. Findings were recapitulated in preclinical models, which demonstrated impaired treatment response to anti–programmed cell death 1 (anti–PD-1)–based therapy in mice receiving a low-fiber diet or probiotics, with a lower frequency of interferon-γ–positive cytotoxic T cells in the tumor microenvironment. Together, these data have clinical implications for patients receiving ICB for cancer.
Christine N. Spencer, Jennifer L. McQuade, Vancheswaran Gopalakrishnan, John A. McCulloch, Marie Vetizou, Alexandria P. Cogdill, Md A. Wadud Khan, Xiaotao Zhang, Michael G. White, Christine B. Peterson, Matthew C. Wong, Golnaz Morad, Theresa Rodgers, Jonathan H. Badger, Beth A. Helmink, Miles C. Andrews, Richard R. Rodrigues, Andrey Morgun, Young S. Kim, Jason Roszik, Kristi Louise Hoffman, Jiali Zheng, Yifan Zhou, Yusra B. Medik, Laura M. Kahn, Sarah Johnson, Courtney W. Hudgens, Khalida Wani, Pierre Olivier Gaudreau, Angela L. Harris, Mohamed A. Jamal, Erez N. Baruch, Eva Perez-Guijarro, Chi Ping Day, Glenn Merlino, Barbara Pazdrak, Brooke S. Lochmann, Robert A. Szczepaniak-Sloane, Reetakshi Arora, Jaime Anderson, Chrystia M. Zobniw, Eliza Posada, Elizabeth Sirmans, Julie Simon, Lauren E. Haydu, Elizabeth M. Burton, Linghua Wang, Minghao Dang, Karen Clise-Dwyer, Sarah Schneider, Thomas Chapman, Nana Ama A.S. Anang, Sheila Duncan, Joseph Toker, Jared C. Malke, Isabella C. Glitza, Rodabe N. Amaria, Hussein A. Tawbi, Adi Diab, Michael K. Wong, Sapna P. Patel, Scott E. Woodman, Michael A. Davies, Merrick I. Ross, Jeffrey E. Gershenwald, Jeffrey E. Lee, Patrick Hwu, Vanessa Jensen, Yardena Samuels, Ravid Straussman, Nadim J. Ajami, Kelly C. Nelson, Luigi Nezi, Joseph F. Petrosino, P. Andrew Futreal, Alexander J. Lazar, Jianhua Hu, Robert R. Jenq, Michael Tetzlaff, Yan Yan, Wendy S. Garrett, Curtis Huttenhower, Padmanee Sharma, Stephanie S. Watowich, James P. Allison, Lorenzo Cohen, Giorgio Trinchieri, Carrie R. Daniel, Jennifer A. Wargo
Mikung Park, Ph.D. and Min Sup Song, Ph.D.
NEAT1 is essential for metabolic changes that promote breast cancer growth and metastasis
Accelerated glycolysis is the main metabolic change observed in cancer, but the underlying molecular mechanisms and their role in cancer progression remain poorly understood. Here, we show that the deletion of the long noncoding RNA (ln-cRNA) Neat1 in MMTV-PyVT mice profoundly impairs tumor initiation, growth, and metastasis, specifically switching off the penultimate step of glycolysis. Mechanistically, NEAT1 directly binds and forms a scaffold bridge for the assembly of PGK1/PGAM1/ENO1 complexes and thereby promotes substrate channeling for high and efficient glycolysis. Notably, NEAT1 is upregulated in cancer patients and correlates with high levels of these complexes, and genetic and pharmacological blockade of penultimate glycolysis ablates NEAT1-dependent tumorigenesis. Finally, we demonstrate that Pinin mediates glucose-stimulated nuclear export of NEAT1, through which it exerts isoform-specific and paraspeckle-independent functions. These findings establish a direct role for NEAT1 in regulating tumor metabolism, provide new insights into the Warburg effect, and identify potential targets for therapy.
Mi Kyung Park, Li Zhang, Kyung Won Min, Jung Hyun Cho, Chih Chen Yeh, Hyesu Moon, Daniel Hormaechea-Agulla, Hyejin Mun, Seungbeom Ko, Ji Won Lee, Sonali Jathar, Aubrey S. Smith, Yixin Yao, Nguyen Thu Giang, Hong Ha Vu, Victoria C. Yan, Mary C. Bridges, Antonis Kourtidis, Florian Muller, Jeong Ho Chang, Su Jung Song, Shinichi Nakagawa, Tetsuro Hirose, Je Hyun Yoon, Min Sup Song
Front (L-R): Mi Kyung Park, Ph.D., James Hwang, M.S.
Instructor, Department of Molecular & Cellular Oncology
Professor, Department of Molecular & Cellular Oncology
Hussein Tawbi, M.D., Ph.D.
Professor, Departments of Melanoma Medical Oncology and Investigational Cancer Therapeutics
Director, Personalized Cancer Therapy Research
Co-Medical Director, Brain Metastasis Clinic
Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma
Background
Lymphocyte-activation gene 3 (LAG-3) and programmed death 1 (PD-1) are distinct inhibitory immune checkpoints that contribute to T-cell exhaustion. The combination of relatlimab, a LAG-3–blocking antibody, and nivolumab, a PD-1–blocking antibody, has been shown to be safe and to have antitumor activity in patients with previously treated melanoma, but the safety and activity in patients with previously untreated melanoma need investigation.
Methods
In this phase 2–3, global, double-blind, randomized trial, we evaluated relatlimab and nivolumab as a fixed-dose combination as compared with nivolumab alone when administered intravenously every 4 weeks to patients with previously untreated metastatic or unresectable melanoma. The primary end point was progression-free survival as assessed by blinded independent central review.
Results
The median progression-free survival was 10.1 months (95% confidence interval [CI], 6.4 to 15.7) with relatlimab–nivolumab as compared with 4.6 months (95% CI, 3.4 to 5.6) with nivolumab (hazard ratio for progression or death, 0.75 [95% CI, 0.62 to 0.92]; P=0.006 by the log-rank test). Progression-free survival at 12 months was 47.7% (95% CI, 41.8 to 53.2) with relatlimab–nivolumab as compared with 36.0% (95% CI, 30.5 to 41.6) with nivolumab. Progression-free survival across key subgroups favored relatlimab–nivolumab over nivolumab. Grade 3 or 4 treatmentrelated adverse events occurred in 18.9% of patients in the relatlimab–nivolumab group and in 9.7% of patients in the nivolumab group.
Conclusions
The inhibition of two immune checkpoints, LAG-3 and PD-1, provided a greater benefit with regard to progression-free survival than inhibition of PD-1 alone in patients with previously untreated metastatic or unresectable melanoma. Relatlimab and nivolumab in combination showed no new safety signals.
Hussein A. Tawbi, M.D., Ph.D., Dirk Schadendorf, M.D., Evan J. Lipson, M.D., Paolo A. Ascierto, M.D., Luis Matamala, M.D., Erika Castillo Gutiérrez, M.D., Piotr Rutkowski, M.D., Ph.D., Helen J. Gogas, M.D., Christopher D. Lao, M.D., M.P.H., Juliana Janoski De Menezes, M.D., Stéphane Dalle, M.D., Ph.D., Ana Arance, M.D., Ph.D., et al., for the RELATIVITY-047 Investigators*
Row 2 (L-R): Lizzy Elisondo, Rachel Trimier, Christine Spillson, Lauren Simpson & Lauren See
Row 3 (L-R): Courtney Powell, Helene Rider, Bonita Joe, Mick Lemoine & Lisa Beal
Row 4 (L-R): Liz Burton, Ysa Coz & Tarin Hennegan
Jason Robert Westin, M.D.
Axicabtagene ciloleucel as second-line therapy for large b-cell lymphoma
Background
The prognosis of patients with early relapsed or refractory large B-cell lymphoma after the receipt of first-line chemoimmunotherapy is poor.
Methods
In this international, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with large B-cell lymphoma that was refractory to or had relapsed no more than 12 months after first-line chemoimmunotherapy to receive axicabta-gene ciloleucel (axi-cel, an autologous anti-CD19 chimeric antigen receptor T-cell therapy) or standard care (two or three cycles of investigator-selected, protocol-defined chemoimmunotherapy, followed by high-dose chemotherapy with autologous stem-cell transplantation in patients with a response to the chemoimmunotherapy). The primary end point was event-free survival accord-ing to blinded central review. Key secondary end points were response and overall survival. Safety was also assessed.
Results
A total of 180 patients were randomly assigned to receive axi-cel and 179 to receive standard care. The primary end-point analysis of event-free survival showed that axi-cel therapy was superior to standard care. At a median follow-up of 24.9 months, the median event-free survival was 8.3 months in the axi-cel group and 2.0 months in the standard-care group, and the 24-month event-free survival was 41% and 16%, respectively (hazard ratio for event or death, 0.40; 95% confidence interval, 0.31 to 0.51; P<0.001). A response occurred in 83% of the patients in the axi-cel group and in 50% of those in the standard-care group (with a complete response in 65% and 32%, respectively). In an interim analysis, the estimated overall survival at 2 years was 61% in the axi-cel group and 52% in the standard-care group. Adverse events of grade 3 or higher occurred in 91% of the patients who received axi-cel and in 83% of those who received standard care. Among patients who received axi-cel, grade 3 or higher cytokine release syndrome occurred in 6% and grade 3 or higher neurologic events in 21%. No deaths related to cytokine release syn-drome or neurologic events occurred.
Conclusions
Axi-cel therapy led to significant improvements, as compared with standard care, in event-free survival and response, with the expected level of high-grade toxic effects.
Frederick L. Locke, M.D., David B. Miklos, M.D., Ph.D., Caron A. Jacobson, M.D., Miguel-Angel Perales, M.D., Marie-José Kersten, M.D., Ph.D., Olalekan O. Oluwole, M.B., B.S., M.D., Armin Ghobadi, M.D., Aaron P. Rapoport, M.D., Joseph McGuirk, D.O., John M. Pagel, M.D., Ph.D., Javier Muñoz, M.D., Umar Farooq, M.D., Tom van Meerten, M.D., Ph.D., Patrick M. Reagan, M.D., Anna Sureda, M.D., Ph.D., Ian W. Flinn, M.D., Ph.D., Peter Vandenberghe, M.D., Ph.D., Kevin W. Song, M.D., Michael Dickinson, M.B., B.S., D.Med.Sci., Monique C. Minnema, M.D., Ph.D., Peter A. Riedell, M.D., Lori A. Leslie, M.D., Sridhar Chaganti, M.D., Yin Yang, M.D., Simone Filosto, Ph.D., Jina Shah, M.D., Marco Schupp, M.D., Christina To, M.D., Paul Cheng, M.D., Ph.D., Leo I. Gordon, M.D., and Jason R. Westin, M.D. for All ZUMA-7 Investigators and Contributing Kite Members
Row 2 (L-R): Jisha Tom, Carolyn Hawkins & Isak Durmic
Row 3 (L-R): Wirt Montinez & Shivon Mathew
Row 4 (L-R): Anuoluwa Ogunlere, Brittani Pulsifer & Jana Lejano
Associate Professor, Department of Lymphoma - Myeloma
Yi Xiao, Ph.D. and Dihua Yu, M.D., Ph.D.
Assistant Professor, Department of Molecular & Cellular Oncology
Professor and Chair Ad Interim, Department of Molecular & Cellular Oncology
Hubert L. and Olive Stringer Distinguished Chair in Basic Science
The allergy mediator histamine confers resistance to immunotherapy in cancer patients via activation of the macrophage histamine receptor H1
Reinvigoration of antitumor immunity remains an unmet challenge. Our retrospective analyses revealed that cancer patients who took antihistamines during immunotherapy treatment had significantly improved survival. We uncovered that histamine and histamine receptor H1 (HRH1) are frequently increased in the tumor microenvironment and induce T cell dysfunction. Mechanistically, HRH1-activated mac-rophages polarize toward an M2-like immunosuppressive phenotype with increased expression of the immune checkpoint VISTA, rendering T cells dysfunctional. HRH1 knockout or antihistamine treatment reverted macro-phage immunosuppression, revitalized T cell cytotoxic function, and restored immunotherapy response. Allergy, via the histamine-HRH1 axis, facilitated tumor growth and induced immunotherapy resistance in mice and humans. Importantly, cancer patients with low plasma histamine levels had a more than tripled objective response rate to anti-PD-1 treatment compared with patients with high plasma histamine. Altogether, pre-existing allergy or high histamine levels in cancer patients can dampen immunotherapy responses and warrant prospectively exploring antihistamines as adjuvant agents for combinatorial immunotherapy.
Hongzhong Li, Yi Xiao, Qin Li, Jun Yao, Xiangliang Yuan, Yuan Zhang, Xuedong Yin, Yohei Saito, Huihui Fan, Ping Li, Wen Ling Kuo, Angela Halpin, Don L. Gibbons, Hideo Yagita, Zhongming Zhao, Da Pang, Guosheng Ren, Cassian Yee, J. Jack Lee, Dihua Yu