Genta, Sofia and Lajkosz, Katherine and Yee, Noelle R. and Spiliopoulou, Pavlina and Heirali, Alya and Hansen, Aaron R. and Siu, Lillian L. and Saibil, Sam and Stayner, Lee-Anne and Yanekina, Maryia and Sauder, Maxwell B. and Keshavarzi, Sareh and Salawu, Abdulazeez and Vornicova, Olga and Butler, Marcus O. and Bedard, Philippe L. and Razak, Albiruni R. Abdul and Rottapel, Robert and Chruscinski, Andrzej and Coburn, Bryan and Spreafico, Anna (2023) Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT). Journal of Experimental and Clinical Cancer Research, 42 (1): 276. ISSN 1756-9966

Abstract

Background:
Immune-checkpoint inhibitors (ICI) can lead to immune-related adverse events (irAEs) in a significant proportion of patients. The mechanisms underlying irAEs development are mostly unknown and might involve multiple immune effectors, such as T cells, B cells and autoantibodies (AutoAb).

Methods:
We used custom autoantigen (AutoAg) microarrays to profile AutoAb related to irAEs in patients receiving ICI. Plasma was collected before and after ICI from cancer patients participating in two clinical trials (NCT03686202, NCT02644369). A one-time collection was obtained from healthy controls for comparison. Custom arrays with 162 autoAg were used to detect IgG and IgM reactivities. Differences of median fluorescent intensity (MFI) were analyzed with Wilcoxon sign rank test and Kruskal–Wallis test. MFI 500 was used as threshold to define autoAb reactivity.

Results:
A total of 114 patients and 14 healthy controls were included in this study. irAEs of grade (G) ≥ 2 occurred in 37/114 patients (32%). We observed a greater number of IgG and IgM reactivities in pre-ICI collections from patients versus healthy controls (62 vs 32 p < 0.001). Patients experiencing irAEs G ≥ 2 demonstrated pre-ICI IgG reactivity to a greater number of AutoAg than patients who did not develop irAEs (39 vs 33 p = 0.040). We observed post-treatment increase of IgM reactivities in subjects experiencing irAEs G ≥ 2 (29 vs 35, p = 0.021) and a decrease of IgG levels after steroids (38 vs 28, p = 0.009).

Conclusions:
Overall, these results support the potential role of autoAb in irAEs etiology and evolution. A prospective study is ongoing to validate our findings (NCT04107311).

People
Genta, Sofia
Author

Genta, Sofia and Lajkosz, Katherine and Yee, Noelle R. and Spiliopoulou, Pavlina and Heirali, Alya and Hansen, Aaron R. and Siu, Lillian L. and Saibil, Sam and Stayner, Lee-Anne and Yanekina, Maryia and Sauder, Maxwell B. and Keshavarzi, Sareh and Salawu, Abdulazeez and Vornicova, Olga and Butler, Marcus O. and Bedard, Philippe L. and Razak, Albiruni R. Abdul and Rottapel, Robert and Chruscinski, Andrzej and Coburn, Bryan and Spreafico, Anna (2023) Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT). Journal of Experimental and Clinical Cancer Research, 42 (1): 276. ISSN 1756-9966

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Lajkosz, Katherine
Author

Genta, Sofia and Lajkosz, Katherine and Yee, Noelle R. and Spiliopoulou, Pavlina and Heirali, Alya and Hansen, Aaron R. and Siu, Lillian L. and Saibil, Sam and Stayner, Lee-Anne and Yanekina, Maryia and Sauder, Maxwell B. and Keshavarzi, Sareh and Salawu, Abdulazeez and Vornicova, Olga and Butler, Marcus O. and Bedard, Philippe L. and Razak, Albiruni R. Abdul and Rottapel, Robert and Chruscinski, Andrzej and Coburn, Bryan and Spreafico, Anna (2023) Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT). Journal of Experimental and Clinical Cancer Research, 42 (1): 276. ISSN 1756-9966

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Yee, Noelle R.
Author

Genta, Sofia and Lajkosz, Katherine and Yee, Noelle R. and Spiliopoulou, Pavlina and Heirali, Alya and Hansen, Aaron R. and Siu, Lillian L. and Saibil, Sam and Stayner, Lee-Anne and Yanekina, Maryia and Sauder, Maxwell B. and Keshavarzi, Sareh and Salawu, Abdulazeez and Vornicova, Olga and Butler, Marcus O. and Bedard, Philippe L. and Razak, Albiruni R. Abdul and Rottapel, Robert and Chruscinski, Andrzej and Coburn, Bryan and Spreafico, Anna (2023) Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT). Journal of Experimental and Clinical Cancer Research, 42 (1): 276. ISSN 1756-9966

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Spiliopoulou, Pavlina
Author

Cartwright, Douglas and Kidd, Andrew C. and Ansel, Sonam and Ascierto, Maria Libera and Spiliopoulou, Pavlina (2025) Oncogenic signalling pathways in cancer immunotherapy: leader or follower in this delicate dance? International Journal of Molecular Sciences, 26 (9): 4393. ISSN 1661-6596

Genta, S. and Araujo, D.V. and Hueniken, K. and Pipinikas, C. and Ventura, R. and Rojas, P. and Jones, G. and Butler, M.O. and Saibil, S.D. and Yu, C. and Easson, A. and Covelli, A. and Sauder, M.B. and Fournier, C. and Saeed Kamil, Z. and Rogalla, P. and Arteaga, D.P. and Vornicova, O. and Spiliopoulou, Pavlina and Muniz, T.P. and Siu, L.L. and Spreafico, A. (2024) Bespoke ctDNA for longitudinal detection of molecular residual disease in high-risk melanoma patients. ESMO Open, 9 (11): 103978. ISSN 2059-7029

Spear, Sarah and Le Saux, Olivia and Mirza, Hasan B. and Iyer, Nayana and Tyson, Katie and Grundland Freile, Fabio and Walton, Josephine B. and Woodman, Chloe and Jarvis, Sheba and Ennis, Darren P. and Aguirre Hernandez, Carmen and Xu, Yuewei and Spiliopoulou, Pavlina and Brenton, James D. and Costa-Pereira, Ana P. and Cook, David P. and Vanderhyden, Barbara C. and Keun, Hector C. and Triantafyllou, Evangelos and Arnold, James N. and McNeish, Iain A. (2024) PTEN loss shapes macrophage dynamics in high grade serous ovarian carcinoma. Cancer Research. ISSN 0008-5472 (In Press)

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Heirali, Alya
Author

Genta, Sofia and Lajkosz, Katherine and Yee, Noelle R. and Spiliopoulou, Pavlina and Heirali, Alya and Hansen, Aaron R. and Siu, Lillian L. and Saibil, Sam and Stayner, Lee-Anne and Yanekina, Maryia and Sauder, Maxwell B. and Keshavarzi, Sareh and Salawu, Abdulazeez and Vornicova, Olga and Butler, Marcus O. and Bedard, Philippe L. and Razak, Albiruni R. Abdul and Rottapel, Robert and Chruscinski, Andrzej and Coburn, Bryan and Spreafico, Anna (2023) Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT). Journal of Experimental and Clinical Cancer Research, 42 (1): 276. ISSN 1756-9966

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Hansen, Aaron R.
Author

Lee, Cha Len and O'Kane, Grainne M. and Mason, Warren P. and Zhang, Wen-Jiang and Spiliopoulou, Pavlina and Hansen, Aaron R. and Grant, Robert C. and Knox, Jennifer J. and Stockley, Tracy L. and Zadeh, Gelareh and Chen, Eric X. (2024) Circulating oncometabolite 2-hydroxyglutarate (2HG) as a potential biomarker for isocitrate dehydrogenase (IDH1/2) mutant cholangiocarcinoma. Molecular Cancer Therapeutics, 23 (3). pp. 394-399. ISSN 1535-7163

Genta, Sofia and Lajkosz, Katherine and Yee, Noelle R. and Spiliopoulou, Pavlina and Heirali, Alya and Hansen, Aaron R. and Siu, Lillian L. and Saibil, Sam and Stayner, Lee-Anne and Yanekina, Maryia and Sauder, Maxwell B. and Keshavarzi, Sareh and Salawu, Abdulazeez and Vornicova, Olga and Butler, Marcus O. and Bedard, Philippe L. and Razak, Albiruni R. Abdul and Rottapel, Robert and Chruscinski, Andrzej and Coburn, Bryan and Spreafico, Anna (2023) Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT). Journal of Experimental and Clinical Cancer Research, 42 (1): 276. ISSN 1756-9966

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Siu, Lillian L.
Author

Genta, Sofia and Lajkosz, Katherine and Yee, Noelle R. and Spiliopoulou, Pavlina and Heirali, Alya and Hansen, Aaron R. and Siu, Lillian L. and Saibil, Sam and Stayner, Lee-Anne and Yanekina, Maryia and Sauder, Maxwell B. and Keshavarzi, Sareh and Salawu, Abdulazeez and Vornicova, Olga and Butler, Marcus O. and Bedard, Philippe L. and Razak, Albiruni R. Abdul and Rottapel, Robert and Chruscinski, Andrzej and Coburn, Bryan and Spreafico, Anna (2023) Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT). Journal of Experimental and Clinical Cancer Research, 42 (1): 276. ISSN 1756-9966

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Saibil, Sam
Author

Genta, Sofia and Lajkosz, Katherine and Yee, Noelle R. and Spiliopoulou, Pavlina and Heirali, Alya and Hansen, Aaron R. and Siu, Lillian L. and Saibil, Sam and Stayner, Lee-Anne and Yanekina, Maryia and Sauder, Maxwell B. and Keshavarzi, Sareh and Salawu, Abdulazeez and Vornicova, Olga and Butler, Marcus O. and Bedard, Philippe L. and Razak, Albiruni R. Abdul and Rottapel, Robert and Chruscinski, Andrzej and Coburn, Bryan and Spreafico, Anna (2023) Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT). Journal of Experimental and Clinical Cancer Research, 42 (1): 276. ISSN 1756-9966

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Stayner, Lee-Anne
Author

Genta, Sofia and Lajkosz, Katherine and Yee, Noelle R. and Spiliopoulou, Pavlina and Heirali, Alya and Hansen, Aaron R. and Siu, Lillian L. and Saibil, Sam and Stayner, Lee-Anne and Yanekina, Maryia and Sauder, Maxwell B. and Keshavarzi, Sareh and Salawu, Abdulazeez and Vornicova, Olga and Butler, Marcus O. and Bedard, Philippe L. and Razak, Albiruni R. Abdul and Rottapel, Robert and Chruscinski, Andrzej and Coburn, Bryan and Spreafico, Anna (2023) Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT). Journal of Experimental and Clinical Cancer Research, 42 (1): 276. ISSN 1756-9966

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Yanekina, Maryia
Author

Genta, Sofia and Lajkosz, Katherine and Yee, Noelle R. and Spiliopoulou, Pavlina and Heirali, Alya and Hansen, Aaron R. and Siu, Lillian L. and Saibil, Sam and Stayner, Lee-Anne and Yanekina, Maryia and Sauder, Maxwell B. and Keshavarzi, Sareh and Salawu, Abdulazeez and Vornicova, Olga and Butler, Marcus O. and Bedard, Philippe L. and Razak, Albiruni R. Abdul and Rottapel, Robert and Chruscinski, Andrzej and Coburn, Bryan and Spreafico, Anna (2023) Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT). Journal of Experimental and Clinical Cancer Research, 42 (1): 276. ISSN 1756-9966

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Sauder, Maxwell B.
Author

Genta, Sofia and Lajkosz, Katherine and Yee, Noelle R. and Spiliopoulou, Pavlina and Heirali, Alya and Hansen, Aaron R. and Siu, Lillian L. and Saibil, Sam and Stayner, Lee-Anne and Yanekina, Maryia and Sauder, Maxwell B. and Keshavarzi, Sareh and Salawu, Abdulazeez and Vornicova, Olga and Butler, Marcus O. and Bedard, Philippe L. and Razak, Albiruni R. Abdul and Rottapel, Robert and Chruscinski, Andrzej and Coburn, Bryan and Spreafico, Anna (2023) Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT). Journal of Experimental and Clinical Cancer Research, 42 (1): 276. ISSN 1756-9966

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Keshavarzi, Sareh
Author

Genta, Sofia and Lajkosz, Katherine and Yee, Noelle R. and Spiliopoulou, Pavlina and Heirali, Alya and Hansen, Aaron R. and Siu, Lillian L. and Saibil, Sam and Stayner, Lee-Anne and Yanekina, Maryia and Sauder, Maxwell B. and Keshavarzi, Sareh and Salawu, Abdulazeez and Vornicova, Olga and Butler, Marcus O. and Bedard, Philippe L. and Razak, Albiruni R. Abdul and Rottapel, Robert and Chruscinski, Andrzej and Coburn, Bryan and Spreafico, Anna (2023) Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT). Journal of Experimental and Clinical Cancer Research, 42 (1): 276. ISSN 1756-9966

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Salawu, Abdulazeez
Author

Genta, Sofia and Lajkosz, Katherine and Yee, Noelle R. and Spiliopoulou, Pavlina and Heirali, Alya and Hansen, Aaron R. and Siu, Lillian L. and Saibil, Sam and Stayner, Lee-Anne and Yanekina, Maryia and Sauder, Maxwell B. and Keshavarzi, Sareh and Salawu, Abdulazeez and Vornicova, Olga and Butler, Marcus O. and Bedard, Philippe L. and Razak, Albiruni R. Abdul and Rottapel, Robert and Chruscinski, Andrzej and Coburn, Bryan and Spreafico, Anna (2023) Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT). Journal of Experimental and Clinical Cancer Research, 42 (1): 276. ISSN 1756-9966

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Vornicova, Olga
Author

Genta, Sofia and Lajkosz, Katherine and Yee, Noelle R. and Spiliopoulou, Pavlina and Heirali, Alya and Hansen, Aaron R. and Siu, Lillian L. and Saibil, Sam and Stayner, Lee-Anne and Yanekina, Maryia and Sauder, Maxwell B. and Keshavarzi, Sareh and Salawu, Abdulazeez and Vornicova, Olga and Butler, Marcus O. and Bedard, Philippe L. and Razak, Albiruni R. Abdul and Rottapel, Robert and Chruscinski, Andrzej and Coburn, Bryan and Spreafico, Anna (2023) Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT). Journal of Experimental and Clinical Cancer Research, 42 (1): 276. ISSN 1756-9966

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Butler, Marcus O.
Author

Genta, Sofia and Lajkosz, Katherine and Yee, Noelle R. and Spiliopoulou, Pavlina and Heirali, Alya and Hansen, Aaron R. and Siu, Lillian L. and Saibil, Sam and Stayner, Lee-Anne and Yanekina, Maryia and Sauder, Maxwell B. and Keshavarzi, Sareh and Salawu, Abdulazeez and Vornicova, Olga and Butler, Marcus O. and Bedard, Philippe L. and Razak, Albiruni R. Abdul and Rottapel, Robert and Chruscinski, Andrzej and Coburn, Bryan and Spreafico, Anna (2023) Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT). Journal of Experimental and Clinical Cancer Research, 42 (1): 276. ISSN 1756-9966

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Bedard, Philippe L.
Author

Genta, Sofia and Lajkosz, Katherine and Yee, Noelle R. and Spiliopoulou, Pavlina and Heirali, Alya and Hansen, Aaron R. and Siu, Lillian L. and Saibil, Sam and Stayner, Lee-Anne and Yanekina, Maryia and Sauder, Maxwell B. and Keshavarzi, Sareh and Salawu, Abdulazeez and Vornicova, Olga and Butler, Marcus O. and Bedard, Philippe L. and Razak, Albiruni R. Abdul and Rottapel, Robert and Chruscinski, Andrzej and Coburn, Bryan and Spreafico, Anna (2023) Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT). Journal of Experimental and Clinical Cancer Research, 42 (1): 276. ISSN 1756-9966

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Razak, Albiruni R. Abdul
Author

Genta, Sofia and Lajkosz, Katherine and Yee, Noelle R. and Spiliopoulou, Pavlina and Heirali, Alya and Hansen, Aaron R. and Siu, Lillian L. and Saibil, Sam and Stayner, Lee-Anne and Yanekina, Maryia and Sauder, Maxwell B. and Keshavarzi, Sareh and Salawu, Abdulazeez and Vornicova, Olga and Butler, Marcus O. and Bedard, Philippe L. and Razak, Albiruni R. Abdul and Rottapel, Robert and Chruscinski, Andrzej and Coburn, Bryan and Spreafico, Anna (2023) Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT). Journal of Experimental and Clinical Cancer Research, 42 (1): 276. ISSN 1756-9966

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Rottapel, Robert
Author

Genta, Sofia and Lajkosz, Katherine and Yee, Noelle R. and Spiliopoulou, Pavlina and Heirali, Alya and Hansen, Aaron R. and Siu, Lillian L. and Saibil, Sam and Stayner, Lee-Anne and Yanekina, Maryia and Sauder, Maxwell B. and Keshavarzi, Sareh and Salawu, Abdulazeez and Vornicova, Olga and Butler, Marcus O. and Bedard, Philippe L. and Razak, Albiruni R. Abdul and Rottapel, Robert and Chruscinski, Andrzej and Coburn, Bryan and Spreafico, Anna (2023) Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT). Journal of Experimental and Clinical Cancer Research, 42 (1): 276. ISSN 1756-9966

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Chruscinski, Andrzej
Author

Genta, Sofia and Lajkosz, Katherine and Yee, Noelle R. and Spiliopoulou, Pavlina and Heirali, Alya and Hansen, Aaron R. and Siu, Lillian L. and Saibil, Sam and Stayner, Lee-Anne and Yanekina, Maryia and Sauder, Maxwell B. and Keshavarzi, Sareh and Salawu, Abdulazeez and Vornicova, Olga and Butler, Marcus O. and Bedard, Philippe L. and Razak, Albiruni R. Abdul and Rottapel, Robert and Chruscinski, Andrzej and Coburn, Bryan and Spreafico, Anna (2023) Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT). Journal of Experimental and Clinical Cancer Research, 42 (1): 276. ISSN 1756-9966

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Coburn, Bryan
Author

Genta, Sofia and Lajkosz, Katherine and Yee, Noelle R. and Spiliopoulou, Pavlina and Heirali, Alya and Hansen, Aaron R. and Siu, Lillian L. and Saibil, Sam and Stayner, Lee-Anne and Yanekina, Maryia and Sauder, Maxwell B. and Keshavarzi, Sareh and Salawu, Abdulazeez and Vornicova, Olga and Butler, Marcus O. and Bedard, Philippe L. and Razak, Albiruni R. Abdul and Rottapel, Robert and Chruscinski, Andrzej and Coburn, Bryan and Spreafico, Anna (2023) Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT). Journal of Experimental and Clinical Cancer Research, 42 (1): 276. ISSN 1756-9966

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Spreafico, Anna
Author

Thakral, Abhinav and Lee, John JW. and Hou, Tianzhichao and Hueniken, Katrina and Dudding, Tom and Gormley, Mark and Virani, Shama and Olshan, Andrew and Diergaarde, Brenda and Ness, Andrew R. and Waterboer, Tim and Smith-Byrne, Karl and Brennan, Paul and Hayes, D. Neil and Sanderson, Eleanor and Brown, M. Catherine and Huang, Sophie and Bratman, Scott V. and Spreafico, Anna and De Almeida, John and Davies, Joel C. and Bierut, Laura and Macfarlane, Gary J. and Lagiou, Pagona and Lagiou, Areti and Polesel, Jerry and Agudo, Antonio and Alemany, Laia and Ahrens, Wolfgang and Healy, Claire M. and Conway, David I. and Nygard, Mari and Canova, Cristina and Holcatova, Ivana and Richiardi, Lorenzo and Znaor, Ariana and Goldstein, David P. and Hung, Rayjean J. and Xu, Wei and Liu, Geoffrey and Espin-Garcia, Osvaldo (2024) Smoking and alcohol by HPV status in head and neck cancer: a Mendelian randomization study. Nature Communications, 15: 7835. ISSN 2041-1723

Spiliopoulou, Pavlina and Lopes, Carlos Diego Holanda and Spreafico, Anna (2024) Promising and minimally invasive biomarkers: targeting melanoma. Cells, 13 (1): 19. ISSN 2073-4409

Genta, Sofia and Lajkosz, Katherine and Yee, Noelle R. and Spiliopoulou, Pavlina and Heirali, Alya and Hansen, Aaron R. and Siu, Lillian L. and Saibil, Sam and Stayner, Lee-Anne and Yanekina, Maryia and Sauder, Maxwell B. and Keshavarzi, Sareh and Salawu, Abdulazeez and Vornicova, Olga and Butler, Marcus O. and Bedard, Philippe L. and Razak, Albiruni R. Abdul and Rottapel, Robert and Chruscinski, Andrzej and Coburn, Bryan and Spreafico, Anna (2023) Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT). Journal of Experimental and Clinical Cancer Research, 42 (1): 276. ISSN 1756-9966

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