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3. Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy

Author

Vellano, Christopher P., White, Michael G., Andrews, Miles C., Chelvanambi, Manoj, Witt, Russell G., Daniele, Joseph R., Titus, Mark, McQuade, Jennifer L., Conforti, Fabio, Burton, Elizabeth M., Lastrapes, Matthew J., Ologun, Gabriel, Cogdill, Alexandria P., Morad, Golnaz, Prieto, Peter, Lazar, Alexander J., Chu, Yanshuo, Han, Guangchun, Khan, M. A. Wadud, Helmink, Beth, Davies, Michael A., Amaria, Rodabe N., Kovacs, Jeffrey J., Woodman, Scott E., Patel, Sapna, Hwu, Patrick, Peoples, Michael, Lee, Jeffrey E., Cooper, Zachary A., Zhu, Haifeng, Gao, Guang, Banerjee, Hiya, Lau, Mike, Gershenwald, Jeffrey E., Lucci, Anthony, Keung, Emily Z., Ross, Merrick I., Pala, Laura, Pagan, Eleonora, Segura, Rossana Lazcano, Liu, Qian, Borthwick, Mikayla S., Lau, Eric, Yates, Melinda S., Westin, Shannon N., Wani, Khalida, Tetzlaff, Michael T., Haydu, Lauren E., Mahendra, Mikhila, Ma, XiaoYan, Logothetis, Christopher, Kulstad, Zachary, Johnson, Sarah, Hudgens, Courtney W., Feng, Ningping, Federico, Lorenzo, Long, Georgina V., Futreal, P. Andrew, Arur, Swathi, Tawbi, Hussein A., Moran, Amy E., Wang, Linghua, Heffernan, Timothy P., Marszalek, Joseph R., and Wargo, Jennifer A.

Published
2022
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4. Multi-modal molecular programs regulate melanoma cell state

Author

Andrews, Miles C., Oba, Junna, Wu, Chang-Jiun, Zhu, Haifeng, Karpinets, Tatiana, Creasy, Caitlin A., Forget, Marie-Andrée, Yu, Xiaoxing, Song, Xingzhi, Mao, Xizeng, Robertson, A. Gordon, Romano, Gabriele, Li, Peng, Burton, Elizabeth M., Lu, Yiling, Sloane, Robert Szczepaniak, Wani, Khalida M., Rai, Kunal, Lazar, Alexander J., Haydu, Lauren E., Bustos, Matias A., Shen, Jianjun, Chen, Yueping, Morgan, Margaret B., Wargo, Jennifer A., Kwong, Lawrence N., Haymaker, Cara L., Grimm, Elizabeth A., Hwu, Patrick, Hoon, Dave S. B., Zhang, Jianhua, Gershenwald, Jeffrey E., Davies, Michael A., Futreal, P. Andrew, Bernatchez, Chantale, and Woodman, Scott E.

Published
2022
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6. Gut microbiota signatures are associated with toxicity to combined CTLA-4 and PD-1 blockade

Author

Andrews, Miles C., Duong, Connie P. M., Gopalakrishnan, Vancheswaran, Iebba, Valerio, Chen, Wei-Shen, Derosa, Lisa, and Khan, Md Abdul Wadud

Subjects
Microbiota (Symbiotic organisms) -- Health aspects, Immunotherapy -- Complications and side effects, Melanoma -- Development and progression -- Care and treatment, Biological sciences, Health
Abstract

Treatment with combined immune checkpoint blockade (CICB) targeting CTLA-4 and PD-1 is associated with clinical benefit across tumor types, but also a high rate of immune-related adverse events. Insights into biomarkers and mechanisms of response and toxicity to CICB are needed. To address this, we profiled the blood, tumor and gut microbiome of 77 patients with advanced melanoma treated with CICB, with a high rate of any [greater than or equal to]grade 3 immune-related adverse events (49%) with parallel studies in pre-clinical models. Tumor-associated immune and genomic biomarkers of response to CICB were similar to those identified for ICB monotherapy, and toxicity from CICB was associated with a more diverse peripheral T-cell repertoire. Profiling of gut microbiota demonstrated a significantly higher abundance of Bacteroides intestinalis in patients with toxicity, with upregulation of mucosal IL-1[beta] in patient samples of colitis and in pre-clinical models. Together, these data offer potential new therapeutic angles for targeting toxicity to CICB. Clinical benefit or intestinal toxicity resulting from combined immune checkpoint blockade in patients with melanoma associates with prevalent commensal bacteria and can be decoupled by IL-1R inhibition., Author(s): Miles C. Andrews [sup.1] [sup.2] [sup.3] , Connie P. M. Duong [sup.4] [sup.5] [sup.6] , Vancheswaran Gopalakrishnan [sup.1] , Valerio Iebba [sup.4] [sup.5] , Wei-Shen Chen [sup.7] [sup.8] , [...]

Published
2021
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7. Author Correction: Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy

Author

Vellano, Christopher P., White, Michael G., Andrews, Miles C., Chelvanambi, Manoj, Witt, Russell G., Daniele, Joseph R., Titus, Mark, McQuade, Jennifer L., Conforti, Fabio, Burton, Elizabeth M., Lastrapes, Matthew J., Ologun, Gabriel, Cogdill, Alexandria P., Morad, Golnaz, Prieto, Peter, Lazar, Alexander J., Chu, Yanshuo, Han, Guangchun, Khan, M. A. Wadud, Helmink, Beth, Davies, Michael A., Amaria, Rodabe N., Kovacs, Jeffrey J., Woodman, Scott E., Patel, Sapna, Hwu, Patrick, Peoples, Michael, Lee, Jeffrey E., Cooper, Zachary A., Zhu, Haifeng, Gao, Guang, Banerjee, Hiya, Lau, Mike, Gershenwald, Jeffrey E., Lucci, Anthony, Keung, Emily Z., Ross, Merrick I., Pala, Laura, Pagan, Eleonora, Segura, Rossana Lazcano, Liu, Qian, Borthwick, Mikayla S., Lau, Eric, Yates, Melinda S., Westin, Shannon N., Wani, Khalida, Tetzlaff, Michael T., Haydu, Lauren E., Mahendra, Mikhila, Ma, XiaoYan, Logothetis, Christopher, Kulstad, Zachary, Johnson, Sarah, Hudgens, Courtney W., Feng, Ningping, Federico, Lorenzo, Long, Georgina V., Futreal, P. Andrew, Arur, Swathi, Tawbi, Hussein A., Moran, Amy E., Wang, Linghua, Heffernan, Timothy P., Marszalek, Joseph R., and Wargo, Jennifer A.

Published
2023
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9. Sustained Type I interferon signaling as a mechanism of resistance to PD-1 blockade

Author

Jacquelot, Nicolas, Yamazaki, Takahiro, Roberti, Maria P., Duong, Connie P. M., Andrews, Miles C., Verlingue, Loic, Ferrere, Gladys, Becharef, Sonia, Vétizou, Marie, Daillère, Romain, Messaoudene, Meriem, Enot, David P., Stoll, Gautier, Ugel, Stefano, Marigo, Ilaria, Foong Ngiow, Shin, Marabelle, Aurélien, Prevost-Blondel, Armelle, Gaudreau, Pierre-Olivier, Gopalakrishnan, Vancheswaran, Eggermont, Alexander M., Opolon, Paule, Klein, Christophe, Madonna, Gabriele, Ascierto, Paolo A., Sucker, Antje, Schadendorf, Dirk, Smyth, Mark J., Soria, Jean-Charles, Kroemer, Guido, Bronte, Vincenzo, Wargo, Jennifer, and Zitvogel, Laurence

Published
2019
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10. Spatially resolved analyses link genomic and immune diversity and reveal unfavorable neutrophil activation in melanoma

Author

Mitra, Akash, Andrews, Miles C., Roh, Whijae, De Macedo, Marianna Petaccia, Hudgens, Courtney W., Carapeto, Fernando, Singh, Shailbala, Reuben, Alexandre, Wang, Feng, Mao, Xizeng, Song, Xingzhi, Wani, Khalida, Tippen, Samantha, Ng, Kwok-Shing, Schalck, Aislyn, Sakellariou-Thompson, Donald A., Chen, Eveline, Reddy, Sangeetha M., Spencer, Christine N., Wiesnoski, Diana, Little, Latasha D., Gumbs, Curtis, Cooper, Zachary A., Burton, Elizabeth M., Hwu, Patrick, Davies, Michael A., Zhang, Jianhua, Bernatchez, Chantale, Navin, Nicholas, Sharma, Padmanee, Allison, James P., Wargo, Jennifer A., Yee, Cassian, Tetzlaff, Michael T., Hwu, Wen-Jen, Lazar, Alexander J., and Futreal, P. Andrew

Published
2020
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11. Stroma remodeling and reduced cell division define durable response to PD-1 blockade in melanoma

Author

Galvani, Elena, Mundra, Piyushkumar A., Valpione, Sara, Garcia-Martinez, Pablo, Smith, Matthew, Greenall, Jonathan, Thakur, Rohit, Helmink, Beth, Andrews, Miles C., Boon, Louis, Chester, Christopher, Gremel, Gabriela, Hogan, Kate, Mandal, Amit, Zeng, Kang, Banyard, Antonia, Ashton, Garry, Cook, Martin, Lorigan, Paul, Wargo, Jennifer A., Dhomen, Nathalie, and Marais, Richard

Published
2020
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12. Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma

Author

Amaria, Rodabe N., Reddy, Sangeetha M., Tawbi, Hussein A., Davies, Michael A., Ross, Merrick I., Glitza, Isabella C., Cormier, Janice N., Lewis, Carol, Hwu, Wen-Jen, Hanna, Ehab, Diab, Adi, Wong, Michael K., Royal, Richard, Gross, Neil, Weber, Randal, Lai, Stephen Y., Ehlers, Richard, Blando, Jorge, Milton, Denái R., Woodman, Scott, Kageyama, Robin, Wells, Daniel K., Hwu, Patrick, Patel, Sapna P., Lucci, Anthony, Hessel, Amy, Lee, Jeffrey E., Gershenwald, Jeffrey, Simpson, Lauren, Burton, Elizabeth M., Posada, Liberty, Haydu, Lauren, Wang, Linghua, Zhang, Shaojun, Lazar, Alexander J., Hudgens, Courtney W., Gopalakrishnan, Vancheswaran, Reuben, Alexandre, Andrews, Miles C., Spencer, Christine N., Prieto, Victor, Sharma, Padmanee, Allison, James, Tetzlaff, Michael T., and Wargo, Jennifer A.

Published
2018
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13. Design, optimisation and standardisation of a high‐dimensional spectral flow cytometry workflow assessing T‐cell immunophenotype in patients with melanoma.

Author

Edwards, Jack M, Andrews, Miles C, Burridge, Hayley, Smith, Robin, Owens, Carole, Edinger, Mark, Pilkington, Katherine, Desfrancois, Juliette, Shackleton, Mark, Senthi, Sashendra, and van Zelm, Menno C

Abstract

Objectives: Despite the success of immune checkpoint blockade, most metastatic melanoma patients fail to respond to therapy or experience severe toxicity. Assessment of biomarkers and immunophenotypes before or early into treatment will help to understand favourable responses and improve therapeutic outcomes. Methods: We present a high‐dimensional approach for blood T‐cell profiling using three multi‐parameter cytometry panels: (1) a TruCount panel for absolute cell counts, (2) a 27‐colour spectral panel assessing T‐cell markers and (3) a 20‐colour spectral panel evaluating intracellular cytokine expression. Pre‐treatment blood mononuclear cells from patients and healthy controls were cryopreserved before staining across 11 batches. Batch effects were tracked using a single‐donor control and the suitability of normalisation was assessed. The data were analysed using manual gating and high‐dimensional strategies. Results: Batch‐to‐batch variation was minimal, as demonstrated by the dimensionality reduction of batch‐control samples, and normalisation did not improve manual or high‐dimensional analysis. Application of the workflow demonstrated the capacity of the panels and showed that patients had fewer lymphocytes than controls (P = 0.0027), due to lower naive CD4+ (P = 0.015) and CD8+ (P = 0.011) T cells and follicular helper T cells (P = 0.00076). Patients showed trends for higher proportions of Ki67 and IL‐2‐expressing cells within CD4+ and CD8+ memory subsets, and increased CD57 and EOMES expression within TCRγδ+ T cells. Conclusion: Our optimised high‐parameter spectral cytometry approach provided in‐depth profiling of blood T cells and found differences in patient immunophenotype at baseline. The robustness of our workflow, as demonstrated by minimal batch effects, makes this approach highly suitable for the longitudinal evaluation of immunotherapy effects. [ABSTRACT FROM AUTHOR]

Published
2023
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14. Targeting endothelin receptor signalling overcomes heterogeneity driven therapy failure

Author

Smith, Michael P, Rowling, Emily J, Miskolczi, Zsofia, Ferguson, Jennifer, Spoerri, Loredana, Haass, Nikolas K, Sloss, Olivia, McEntegart, Sophie, Arozarena, Imanol, von Kriegsheim, Alex, Rodriguez, Javier, Brunton, Holly, Kmarashev, Jivko, Levesque, Mitchell P, Dummer, Reinhard, Frederick, Dennie T, Andrews, Miles C, Cooper, Zachary A, Flaherty, Keith T, Wargo, Jennifer A, and Wellbrock, Claudia

Published
2017
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15. Immune-related adverse events secondary to immunotherapy in oncology.

Author

Hui-Ling Yeoh, Freilich, Karen, Voskoboynik, Mark, Moore, Maggie, Andrews, Miles C., Shackleton, Mark, and Haydon, Andrew M.

Subjects
DRUG side effects, IMMUNOTHERAPY, ONCOLOGY, CANCER prognosis
Abstract

Background Immunotherapy has reshaped the prognoses for many cancers and is increasingly used in both metastatic and adjuvant settings. There is a high prevalence of immunotherapy side effects, or immune-related adverse events (irAEs), which can affect any organ. Some irAEs can cause permanent or prolonged morbidity and, in rare cases, may be fatal. irAEs can present with mild, non-specific symptoms, resulting in delays to identification and management. Objective We aim to provide a general overview of immunotherapy and irAEs, highlighting common clinical scenarios and general principles of management. Discussion Cancer immunotherapy toxicity is an important clinical problem that is increasingly relevant to general practice, where patients with adverse events may first present. Early diagnosis and timely intervention are important in limiting the severity and morbidity of these toxicities. The management of irAEs should follow treatment guidelines, in consultation with patients’ treating oncology teams. [ABSTRACT FROM AUTHOR]

Published
2023
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16. Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy

Author

Vellano, C, White, M, Andrews, M, Chelvanambi, M, Witt, R, Daniele, J, Titus, M, Mcquade, J, Conforti, F, Burton, E, Lastrapes, M, Ologun, G, Cogdill, A, Morad, G, Prieto, P, Lazar, A, Chu, Y, Han, G, Khan, M, Helmink, B, Davies, M, Amaria, R, Kovacs, J, Woodman, S, Patel, S, Hwu, P, Peoples, M, Lee, J, Cooper, Z, Zhu, H, Gao, G, Banerjee, H, Lau, M, Gershenwald, J, Lucci, A, Keung, E, Ross, M, Pala, L, Pagan, E, Segura, R, Liu, Q, Borthwick, M, Lau, E, Yates, M, Westin, S, Wani, K, Tetzlaff, M, Haydu, L, Mahendra, M, Ma, X, Logothetis, C, Kulstad, Z, Johnson, S, Hudgens, C, Feng, N, Federico, L, Long, G, Futreal, P, Arur, S, Tawbi, H, Moran, A, Wang, L, Heffernan, T, Marszalek, J, Wargo, J, Vellano, Christopher P., White, Michael G., Andrews, Miles C., Chelvanambi, Manoj, Witt, Russell G., Daniele, Joseph R., Titus, Mark, McQuade, Jennifer L., Conforti, Fabio, Burton, Elizabeth M., Lastrapes, Matthew J., Ologun, Gabriel, Cogdill, Alexandria P., Morad, Golnaz, Prieto, Peter, Lazar, Alexander J., Chu, Yanshuo, Han, Guangchun, Khan, M. A. Wadud, Helmink, Beth, Davies, Michael A., Amaria, Rodabe N., Kovacs, Jeffrey J., Woodman, Scott E., Patel, Sapna, Hwu, Patrick, Peoples, Michael, Lee, Jeffrey E., Cooper, Zachary A., Zhu, Haifeng, Gao, Guang, Banerjee, Hiya, Lau, Mike, Gershenwald, Jeffrey E., Lucci, Anthony, Keung, Emily Z., Ross, Merrick I., Pala, Laura, Pagan, Eleonora, Segura, Rossana Lazcano, Liu, Qian, Borthwick, Mikayla S., Lau, Eric, Yates, Melinda S., Westin, Shannon N., Wani, Khalida, Tetzlaff, Michael T., Haydu, Lauren E., Mahendra, Mikhila, Ma, XiaoYan, Logothetis, Christopher, Kulstad, Zachary, Johnson, Sarah, Hudgens, Courtney W., Feng, Ningping, Federico, Lorenzo, Long, Georgina V., Futreal, P. Andrew, Arur, Swathi, Tawbi, Hussein A., Moran, Amy E., Wang, Linghua, Heffernan, Timothy P., Marszalek, Joseph R., Wargo, Jennifer A., Vellano, C, White, M, Andrews, M, Chelvanambi, M, Witt, R, Daniele, J, Titus, M, Mcquade, J, Conforti, F, Burton, E, Lastrapes, M, Ologun, G, Cogdill, A, Morad, G, Prieto, P, Lazar, A, Chu, Y, Han, G, Khan, M, Helmink, B, Davies, M, Amaria, R, Kovacs, J, Woodman, S, Patel, S, Hwu, P, Peoples, M, Lee, J, Cooper, Z, Zhu, H, Gao, G, Banerjee, H, Lau, M, Gershenwald, J, Lucci, A, Keung, E, Ross, M, Pala, L, Pagan, E, Segura, R, Liu, Q, Borthwick, M, Lau, E, Yates, M, Westin, S, Wani, K, Tetzlaff, M, Haydu, L, Mahendra, M, Ma, X, Logothetis, C, Kulstad, Z, Johnson, S, Hudgens, C, Feng, N, Federico, L, Long, G, Futreal, P, Arur, S, Tawbi, H, Moran, A, Wang, L, Heffernan, T, Marszalek, J, Wargo, J, Vellano, Christopher P., White, Michael G., Andrews, Miles C., Chelvanambi, Manoj, Witt, Russell G., Daniele, Joseph R., Titus, Mark, McQuade, Jennifer L., Conforti, Fabio, Burton, Elizabeth M., Lastrapes, Matthew J., Ologun, Gabriel, Cogdill, Alexandria P., Morad, Golnaz, Prieto, Peter, Lazar, Alexander J., Chu, Yanshuo, Han, Guangchun, Khan, M. A. Wadud, Helmink, Beth, Davies, Michael A., Amaria, Rodabe N., Kovacs, Jeffrey J., Woodman, Scott E., Patel, Sapna, Hwu, Patrick, Peoples, Michael, Lee, Jeffrey E., Cooper, Zachary A., Zhu, Haifeng, Gao, Guang, Banerjee, Hiya, Lau, Mike, Gershenwald, Jeffrey E., Lucci, Anthony, Keung, Emily Z., Ross, Merrick I., Pala, Laura, Pagan, Eleonora, Segura, Rossana Lazcano, Liu, Qian, Borthwick, Mikayla S., Lau, Eric, Yates, Melinda S., Westin, Shannon N., Wani, Khalida, Tetzlaff, Michael T., Haydu, Lauren E., Mahendra, Mikhila, Ma, XiaoYan, Logothetis, Christopher, Kulstad, Zachary, Johnson, Sarah, Hudgens, Courtney W., Feng, Ningping, Federico, Lorenzo, Long, Georgina V., Futreal, P. Andrew, Arur, Swathi, Tawbi, Hussein A., Moran, Amy E., Wang, Linghua, Heffernan, Timothy P., Marszalek, Joseph R., and Wargo, Jennifer A.

Abstract

Treatment with therapy targeting BRAF and MEK (BRAF/MEK) has revolutionized care in melanoma and other cancers; however, therapeutic resistance is common and innovative treatment strategies are needed1,2. Here we studied a group of patients with melanoma who were treated with neoadjuvant BRAF/MEK-targeted therapy (NCT02231775, n = 51) and observed significantly higher rates of major pathological response (MPR; ≤10% viable tumour at resection) and improved recurrence-free survival (RFS) in female versus male patients (MPR, 66% versus 14%, P = 0.001; RFS, 64% versus 32% at 2 years, P = 0.021). The findings were validated in several additional cohorts2–4 of patients with unresectable metastatic melanoma who were treated with BRAF- and/or MEK-targeted therapy (n = 664 patients in total), demonstrating improved progression-free survival and overall survival in female versus male patients in several of these studies. Studies in preclinical models demonstrated significantly impaired anti-tumour activity in male versus female mice after BRAF/MEK-targeted therapy (P = 0.006), with significantly higher expression of the androgen receptor in tumours of male and female BRAF/MEK-treated mice versus the control (P = 0.0006 and P = 0.0025). Pharmacological inhibition of androgen receptor signalling improved responses to BRAF/MEK-targeted therapy in male and female mice (P = 0.018 and P = 0.003), whereas induction of androgen receptor signalling (through testosterone administration) was associated with a significantly impaired response to BRAF/MEK-targeted therapy in male and female patients (P = 0.021 and P < 0.0001). Together, these results have important implications for therapy.

Published
2022

17. Characterization of the treatment-naive immune microenvironment in melanoma with BRAF mutation

Author

Wang, Minyu, primary, Zadeh, Soroor, additional, Pizzolla, Angela, additional, Thia, Kevin, additional, Gyorki, David E, additional, McArthur, Grant A, additional, Scolyer, Richard A, additional, Long, Georgina, additional, Wilmott, James S, additional, Andrews, Miles C, additional, Au-Yeung, George, additional, Weppler, Ali, additional, Sandhu, Shahneen, additional, Trapani, Joseph A, additional, Davis, Melissa J, additional, and Neeson, Paul Joseph, additional

Published
2022
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18. Author Correction: Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma

Author

Amaria, Rodabe N., Reddy, Sangeetha M., Tawbi, Hussein A., Davies, Michael A., Ross, Merrick I., Glitza, Isabella C., Cormier, Janice N., Lewis, Carol, Hwu, Wen-Jen, Hanna, Ehab, Diab, Adi, Wong, Michael K., Royal, Richard, Gross, Neil, Weber, Randal, Lai, Stephen Y., Ehlers, Richard, Blando, Jorge, Milton, Denái R., Woodman, Scott, Kageyama, Robin, Wells, Daniel K., Hwu, Patrick, Patel, Sapna P., Lucci, Anthony, Hessel, Amy, Lee, Jeffrey E., Gershenwald, Jeffrey, Simpson, Lauren, Burton, Elizabeth M., Posada, Liberty, Haydu, Lauren, Wang, Linghua, Zhang, Shaojun, Lazar, Alexander J., Hudgens, Courtney W., Gopalakrishnan, Vancheswaran, Reuben, Alexandre, Andrews, Miles C., Spencer, Christine N., Prieto, Victor, Sharma, Padmanee, Allison, James, Tetzlaff, Michael T., and Wargo, Jennifer A.

Published
2018
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19. Publisher Correction: Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma

Author

Amaria, Rodabe N., Reddy, Sangeetha M., Tawbi, Hussein A., Davies, Michael A., Ross, Merrick I., Glitza, Isabella C., Cormier, Janice N., Lewis, Carol, Hwu, Wen-Jen, Hanna, Ehab, Diab, Adi, Wong, Michael K., Royal, Richard, Gross, Neil, Weber, Randal, Lai, Stephen Y., Ehlers, Richard, Blando, Jorge, Milton, Denái R., Woodman, Scott, Kageyama, Robin, Wells, Daniel K., Hwu, Patrick, Patel, Sapna P., Lucci, Anthony, Hessel, Amy, Lee, Jeffrey E., Gershenwald, Jeffrey, Simpson, Lauren, Burton, Elizabeth M., Posada, Liberty, Haydu, Lauren, Wang, Linghua, Zhang, Shaojun, Lazar, Alexander J., Hudgens, Courtney W., Gopalakrishnan, Vancheswaran, Reuben, Alexandre, Andrews, Miles C., Spencer, Christine N., Prieto, Victor, Sharma, Padmanee, Allison, James, Tetzlaff, Michael T., and Wargo, Jennifer A.

Published
2018
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20. Identification of MicroRNA–mRNA Networks in Melanoma and Their Association with PD-1 Checkpoint Blockade Outcomes

Author

Sloane, Robert A. Szczepaniak, primary, White, Michael G., additional, Witt, Russell G., additional, Banerjee, Anik, additional, Davies, Michael A., additional, Han, Guangchun, additional, Burton, Elizabeth, additional, Ajami, Nadim, additional, Simon, Julie M., additional, Bernatchez, Chantale, additional, Haydu, Lauren E., additional, Tawbi, Hussein A., additional, Gershenwald, Jeffrey E., additional, Keung, Emily, additional, Ross, Merrick, additional, McQuade, Jennifer, additional, Amaria, Rodabe N., additional, Wani, Khalida, additional, Lazar, Alexander J., additional, Woodman, Scott E., additional, Wang, Linghua, additional, Andrews, Miles C., additional, and Wargo, Jennifer A., additional

Published
2021
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21. Short-term treatment with multi-drug regimens combining BRAF/MEK-targeted therapy and immunotherapy results in durable responses in Braf-mutated melanoma

Author

White, Michael G., primary, Szczepaniak Sloane, Robert, additional, Witt, Russell G., additional, Reuben, Alexandre, additional, Gaudreau, Pierre Olivier, additional, Andrews, Miles C., additional, Feng, Ningping, additional, Johnson, Sarah, additional, Class, Caleb A., additional, Bristow, Christopher, additional, Wani, Khalida, additional, Hudgens, Courtney, additional, Nezi, Luigi, additional, Manzo, Teresa, additional, De Macedo, Mariana Pettaccia, additional, Hu, Jianhua, additional, Davis, Richard, additional, Jiang, Hong, additional, Prieto, Peter, additional, Burton, Elizabeth, additional, Hwu, Patrick, additional, Tawbi, Hussein, additional, Gershenwald, Jeffrey, additional, Lazar, Alexander J., additional, Tetzlaff, Michael T., additional, Overwijk, Willem, additional, Woodman, Scott E, additional, Cooper, Zachary A., additional, Marszalek, Joseph R., additional, Davies, Michael A., additional, Heffernan, Timothy P., additional, and Wargo, Jennifer A., additional

Published
2021
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22. Abstract 2838: The gut microbiome (GM) and immunotherapy response are influenced by host lifestyle factors

Author

Spencer, Christine N., primary, Gopalakrishnan, Vancheswaran, additional, McQuade, Jennifer, additional, Andrews, Miles C., additional, Helmink, Beth, additional, Khan, M.A. Wadud, additional, Sirmans, Elizabeth, additional, Haydu, Lauren, additional, Cogdill, Alexandria, additional, Burton, Elizabeth, additional, Amaria, Rodabe, additional, Patel, Sapna, additional, Glitza, Isabella, additional, Davies, MIchael, additional, Posada, Eliza, additional, Hwu, Wen-Jen, additional, Diab, Adi, additional, Nelson, Kelly, additional, Tawbi, Hussein, additional, Wong, Michael, additional, Jenq, Robert R., additional, Cohen, Lorenzo, additional, Daniel-MacDougall, Carrie, additional, and Wargo, Jennifer A., additional

Published
2019
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24. The RNA-binding Protein MEX3B Mediates Resistance to Cancer Immunotherapy by Downregulating HLA-A Expression

Author

Huang, Lu, primary, Malu, Shruti, additional, McKenzie, Jodi A., additional, Andrews, Miles C., additional, Talukder, Amjad H., additional, Tieu, Trang, additional, Karpinets, Tatiana, additional, Haymaker, Cara, additional, Forget, Marie-Andrée, additional, Williams, Leila J., additional, Wang, Zhe, additional, Mbofung, Rina M., additional, Wang, Zhi-Qiang, additional, Davis, Richard Eric, additional, Lo, Roger S., additional, Wargo, Jennifer A., additional, Davies, Michael A., additional, Bernatchez, Chantale, additional, Heffernan, Timothy, additional, Amaria, Rodabe N., additional, Korkut, Anil, additional, Peng, Weiyi, additional, Roszik, Jason, additional, Lizée, Gregory, additional, Woodman, Scott E., additional, and Hwu, Patrick, additional

Published
2018
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26. Autoantibodies May Predict Immune-Related Toxicity: Results from a Phase I Study of Intralesional Bacillus Calmette–Guérin followed by Ipilimumab in Patients with Advanced Metastatic Melanoma

Author

Da Gama Duarte, Jessica, primary, Parakh, Sagun, additional, Andrews, Miles C., additional, Woods, Katherine, additional, Pasam, Anupama, additional, Tutuka, Candani, additional, Ostrouska, Simone, additional, Blackburn, Jonathan M., additional, Behren, Andreas, additional, and Cebon, Jonathan, additional

Published
2018
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28. Abstract CT156: Novel neoadjuvant targeted therapy trial yields insight into molecular mechanisms of response

Author

Woodman, Scott E., primary, Prieto, Peter, additional, Andrews, Miles C., additional, Amaria, Rodabe N., additional, Tetzlaff, Michael, additional, Diab, Adi, additional, Patel, Sapna P., additional, Wen-Jen, Hwu, additional, Glitza, Isabella, additional, Tawbi, Hussein, additional, Hwu, Patrick, additional, Cormier, Janice, additional, Lucci, Anthony, additional, Royal, Richard, additional, Lee, Jeffrey, additional, Bassett, Roland, additional, Simpson, Lauren, additional, Burton, Elizabeth, additional, Zhao, Li, additional, Grimm, Elizabeth, additional, Reuben, Alexandre, additional, Spencer, Christine, additional, Oba, Junna, additional, Ross, Merrick, additional, Gershenwald, Jeffrey, additional, Davies, Michael, additional, and Wargo, Jennifer A., additional

Published
2017
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31. Efficacy of anti-PD-1 therapy in patients with melanoma brain metastases

Author

Parakh, Sagun, primary, Park, John J, additional, Mendis, Shehara, additional, Rai, Rajat, additional, Xu, Wen, additional, Lo, Serigne, additional, Drummond, Martin, additional, Rowe, Catherine, additional, Wong, Annie, additional, McArthur, Grant, additional, Haydon, Andrew, additional, Andrews, Miles C, additional, Cebon, Jonathan, additional, Guminski, Alex, additional, Kefford, Richard F, additional, Long, Georgina V, additional, Menzies, Alexander M, additional, Klein, Oliver, additional, and Carlino, Matteo S, additional

Published
2017
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32. Reply to ‘Comment on ‘Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy’’

Author

Bowyer, Samantha, primary, Prithviraj, Prashanth, additional, Lorigan, Paul, additional, Larkin, James, additional, McArthur, Grant, additional, Atkinson, Victoria, additional, Millward, Michael, additional, Khou, Muoi, additional, Diem, Stefan, additional, Ramanujam, Sangeetha, additional, Kong, Ben, additional, Liniker, Elizabeth, additional, Guminski, Alexander, additional, Parente, Phillip, additional, Andrews, Miles C, additional, Parakh, Sagun, additional, Cebon, Jonathan, additional, Long, Georgina V, additional, Carlino, Matteo S, additional, and Klein, Oliver, additional

Published
2017
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38. Longitudinal analysis of the gut microbiota during anti-PD-1 therapy reveals stable microbial features of response in melanoma patients.

Author

Macandog ADG, Catozzi C, Capone M, Nabinejad A, Nanaware PP, Liu S, Vinjamuri S, Stunnenberg JA, Galiè S, Jodice MG, Montani F, Armanini F, Cassano E, Madonna G, Mallardo D, Mazzi B, Pece S, Tagliamonte M, Vanella V, Barberis M, Ferrucci PF, Blank CU, Bouvier M, Andrews MC, Xu X, Santambrogio L, Segata N, Buonaguro L, Cocorocchio E, Ascierto PA, Manzo T, and Nezi L

Abstract

Immune checkpoint inhibitors (ICIs) improve outcomes in advanced melanoma, but many patients are refractory or experience relapse. The gut microbiota modulates antitumor responses. However, inconsistent baseline predictors point to heterogeneity in responses and inadequacy of cross-sectional data. We followed patients with unresectable melanoma from baseline and during anti-PD-1 therapy, collecting fecal and blood samples that were surveyed for changes in the gut microbiota and immune markers. Varying patient responses were linked to different gut microbiota dynamics during ICI treatment. We select complete responders by their stable microbiota functions and validate them using multiple external cohorts and experimentally. We identify major histocompatibility complex class I (MHC class I)-restricted peptides derived from flagellin-related genes of Lachnospiraceae (FLach) as structural homologs of tumor-associated antigens, detect FLach-reactive CD8 + T cells in complete responders before ICI therapy, and demonstrate that FLach peptides improve antitumor immunity. These findings highlight the prognostic value of microbial functions and therapeutic potential of tumor-mimicking microbial peptides., Competing Interests: Declaration of interests L.N., T.M., P.A.A., and A.D.G.M. are named co-inventors on a patent application relating to this work (EP n. 24164184.4 “Flagellin-related peptides and uses”). M.C.A. reports advisory board participation, honoraria, or research funds to institutions from MSD Australia, BMS Australia, and Pierre Fabre Australia and is a named co-inventor on a patent application relating to Methods and compositions for treating cancer (WO2020106983A1), all unrelated to this work. P.A.A. reports grants or contracts from Bristol Myers Squibb, Roche-Genentech, Pfizer, and Sanofi; consulting fees from Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Merck Serono, Pierre Fabre, Sun Pharma, Sanofi, Sandoz, Italfarmaco, Nektar, Pfizer, Lunaphore, Medicenna, Bio-Al Health, ValoTx, Replimmune, and Bayer; support for attending meetings and/or travel from Pfizer, Bio-Al Health, and Replimmune; and participating on a data safety monitoring board or advisory board for Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, AstraZeneca, Boehringer Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Oncosec, Nouscom, Seagen, iTeos, and Erasca. L.N. reports research funds from BMS Europe unrelated to this work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2024
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