Ascites and resistance to immune checkpoint inhibition in dMMR/MSI-H metastatic colorectal and gastric cancers
Open accessAbstract
Background: Despite unprecedented benefit from immune checkpoint inhibitors (ICIs) in patients with mismatch repair deficient (dMMR)/microsatellite instability high (MSI-H) advanced gastrointestinal cancers, a relevant proportion of patients shows primary resistance or short-term disease control. Since malignant effusions represent an immune-suppressed niche, we investigated whether peritoneal involvement with or without ascites is a poor prognostic factor in patients with dMMR/MSI-H metastatic colorectal cancer (mCRC) and gastric cancer (mGC) receiving ICIs. Methods: We conducted a global multicohort study at Tertiary Cancer Centers and collected clinic-pathological data from a cohort of patients with dMMR/MSI-H mCRC treated with anti-PD-(L)1 ±anti-CTLA-4 agents at 12 institutions (developing set). A cohort of patients with dMMR/MSI-high mGC treated with anti-PD-1 agents±chemotherapy at five institutions was used as validating dataset. Results: The mCRC cohort included 502 patients. After a median follow-up of 31.2 months, patients without peritoneal metastases and those with peritoneal metastases and no ascites had similar outcomes (adjusted HR (aHR) 1.15, 95% CI 0.85 to 1.56 for progression-free survival (PFS); aHR 0.96, 95% CI 0.65 to 1.42 for overall survival (OS)), whereas inferior outcomes were observed in patients with peritoneal metastases and ascites (aHR 2.90, 95% CI 1.70 to 4.94; aHR 3.33, 95% CI 1.88 to 5.91) compared with patients without peritoneal involvement. The mGC cohort included 59 patients. After a median follow-up of 17.4 months, inferior PFS and OS were reported in patients with peritoneal metastases and ascites (aHR 3.83, 95% CI 1.68 to 8.72; aHR 3.44, 95% CI 1.39 to 8.53, respectively), but not in patients with only peritoneal metastases (aHR 1.87, 95% CI 0.64 to 5.46; aHR 2.15, 95% CI 0.64 to 7.27) when compared with patients without peritoneal involvement. Conclusions: Patients with dMMR/MSI-H gastrointestinal cancers with peritoneal metastases and ascites should be considered as a peculiar subgroup with highly unfavorable outcomes to current ICI-based therapies. Novel strategies to target the immune-suppressive niche in malignant effusions should be investigated, as well as next-generation ICIs or intraperitoneal approaches.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The association between peritoneal metastases/ascites and poorer outcomes in dMMR/MSI-H mCRC treated with ICIs has been attributed to the presence of an immune-suppressive environment within serous cavities, potentially hindering the efficacy of immunotherapy.
“This association has been attributed to the presence of an immune-suppressive environment within serous cavities, potentially hindering the efficacy of immunotherapy [165].”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [165]
In a cohort of 502 patients with dMMR/MSI-H mCRC treated with ICIs, the presence of peritoneal metastases and ascites correlated with poorer outcomes.
“Their findings revealed that the presence of peritoneal metastases and ascites correlated with poorer outcomes in a cohort of 502 patients with dMMR/MSI-H mCRC treated with ICIs.”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [165]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade
Le, D. T., Durham, J. N., Smith, K. N., Wang, H., Bartlett, B. R., Aulakh, L. K., Lu, S., Kemberling, H., Wilt, C., Luber, B. S., et al. (2017) · Science · doi:10.1126/science.aan6733 · Cited by 6,645 · see citing works
Janjigian, Y. Y., Shitara, K., Moehler, M. H., Marcelo Garrido, S., Salman, P., Shen, L., Wyrwicz, L. S., Yamaguchi, K., Skoczylas, T., Bragagnoli, A. S. C., et al. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00797-2 · Cited by 3,104 · see citing works
Self-citationPembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer
André, T., Shiu, K.-K., Kim, T. W., Jensen, B. V., Jensen, L. H., Punt, C., Smith, D., Garcia-Carbonero, R., Benavides, M., Gibbs, P., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2017699 · Cited by 3,099 · see citing works
Self-citationOverman, M. J., McDermott, R., Leach, J. L., Lonardi, S., Lenz, H.-J., Morse, M. A., Desai, J., Hill, A., Axelson, M., Moss, R. A., et al. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30422-9 · Cited by 2,836 · see citing works
Self-citationShitara, K., Özgüroğlu, M., Bang, Y., Bartolomeo, M. D., Mandalà, M., Ryu, M., Fornaro, L., Olesiński, T., Caglevic, C., Chung, H. C., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)31257-1 · Cited by 1,290 · see citing works
Self-citationShitara, K., Cutsem, E. V., Bang, Y., Fuchs, C. S., Wyrwicz, L. S., Lee, K., Kudaba, I., Marcelo Garrido, S., Chung, H. C., Lee, J., et al. (2020) · JAMA Oncology · doi:10.1001/jamaoncol.2020.3370 · Cited by 1,145 · see citing works
Self-citationLuchini, C., Bibeau, F., Ligtenberg, M. J. L., Singh, N., Nottegar, A., Bosse, T., Miller, R. E., Riaz, N., Douillard, J.-Y., André, F., et al. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz116 · Cited by 1,044 · see citing works
Le, D. T., Kim, T. W., Van Cutsem, E., Geva, R., Jäger, D., Hara, H., Burge, M., O’Neil, B., Kavan, P., Yoshino, T., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.19.02107 · Cited by 1,005 · see citing works
Schrock, A. B., Ouyang, C., Sandhu, J. S., Sokol, E. S., Jin, D. X., Ross, J. S., Miller, V. A., Lim, D. W., Amanam, I. U., Chao, J., et al. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz134 · Cited by 620 · see citing works
Self-citationChao, J., Fuchs, C. S., Shitara, K., et al. (2021) · JAMA Oncology · doi:10.1001/jamaoncol.2021.0275 · Cited by 442 · see citing works
Self-citationPrimary and metastatic peritoneal surface malignancies
Guiral, D. C., Hübner, M., Alyami, M. S., Bhatt, A., Ceelen, W. P., Gléhen, O., Lordick, F., Ramsay, R. G., Sgarbura, O. A., der Speeten, K. V., et al. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-021-00326-6 · Cited by 323 · see citing works
Cohen, R., Hain, É., Buhard, O., Guilloux, A., Bardier–Dupas, A., Kaci, R., Bertheau, P., Renaud, F., Bibeau, F., Fléjou, J., et al. (2018) · JAMA Oncology · doi:10.1001/jamaoncol.2018.4942 · Cited by 248 · see citing works
Self-citationKwon, M., An, M., Klempner, S. J., Lee, H., Kim, K., Sa, J. K., Cho, H. J., Hong, J. Y., Lee, T., Min, Y. W., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-0219 · Cited by 238 · see citing works
Self-citationClinical features and survival of lung cancer patients with pleural effusions
Porcel, J. M., Gasol, A., Bielsa, S., et al. (2015) · Respirology · doi:10.1111/resp.12496 · Cited by 232 · see citing works
Pietrantonio, F., Randon, G., Bartolomeo, M. D., Luciani, A., Chao, J., Smyth, E. C., & Petrelli, F. (2021) · ESMO Open · doi:10.1016/j.esmoop.2020.100036 · Cited by 188 · see citing works
Self-citationTim-4+ cavity-resident macrophages impair anti-tumor CD8+ T cell immunity
Chow, A. T., Schad, S. E., Green, M. D., Hellmann, M. D., Allaj, V., Ceglia, N., Zago, G., Shah, N., Sharma, S. K., Mattar, M. S., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.05.006 · Cited by 183 · see citing works
Wang, R., Song, S., Harada, K., Amlashi, F. G., Badgwell, B. D., Pizzi, M. P., Xu, Y., Zhao, W., Dong, X., Jin, J., et al. (2019) · Gut · doi:10.1136/gutjnl-2018-318070 · Cited by 164 · see citing works
Buechler, M. B., Kim, K.-W., Onufer, E. J., Williams, J. W., Little, C. C., Dominguez, C. X., Li, Q., Sandoval, W. N., Cooper, J. E., Harris, C. A., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.05.010 · Cited by 161 · see citing works
Corti, F., Lonardi, S., Intini, R., Salati, M., Fenocchio, E., Belli, C., Borelli, B., Brambilla, M., Prete, A. A., Quarà, V., et al. (2021) · European Journal of Cancer · doi:10.1016/j.ejca.2021.03.043 · Cited by 116 · see citing works
Self-citationTanaka, Y., Chiwaki, F., Kojima, S., Kawazu, M., Komatsu, M., Ueno, T., Inoue, S., Sekine, S., Matsusaki, K., Matsushita, H., et al. (2021) · Nature Cancer · doi:10.1038/s43018-021-00240-6 · Cited by 104 · see citing works
Making cold malignant pleural effusions hot: driving novel immunotherapies
Murthy, P., Ekeke, C. N., Russell, K. L., Butler, S. C., Wang, Y., Luketich, J. D., Soloff, A. C., Dhupar, R., & Lotze, M. T. (2019) · OncoImmunology · doi:10.1080/2162402x.2018.1554969 · Cited by 80 · see citing works
Colle, R., Radzik, A., Cohen, R., Pellat, A., López‐Trabada, D., Cachanado, M., Duval, A., Svrcek, M., Menu, Y., & André, T. (2020) · European Journal of Cancer · doi:10.1016/j.ejca.2020.11.009 · Cited by 70 · see citing works
Self-citationTreatment of malignant pleural effusions: the case for localized immunotherapy
Donnenberg, A. D., Luketich, J. D., Dhupar, R., et al. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0590-4 · Cited by 68 · see citing works
Pietrantonio, F., Loupakis, F., Randon, G., Raimondi, A., Salati, M., Trapani, D., Pagani, F., Depetris, I., Maddalena, G., Morano, F., et al. (2020) · The Oncologist · doi:10.1634/theoncologist.2020-0014 · Cited by 51 · see citing works
Self-citationPietrantonio, F., Miceli, R., Rimassa, L., Lonardi, S., Aprile, G., Mennitto, A., Marmorino, F., Bozzarelli, S., Antonuzzo, L., Tamburini, E., et al. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw627 · Cited by 50 · see citing works
Self-citationFucà, G., Corti, F., Ambrosini, M., Intini, R., Salati, M., Fenocchio, E., Manca, P., Manai, C., Daniel, F., Raimondi, A., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-002501 · Cited by 31 · see citing works
Self-citationMarabelle, A., Cassier, P. A., Fakih, M., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.2020.38.15_suppl.4020 · Cited by 29 · see citing works
Self-citationPietrantonio, F., Lonardi, S., Corti, F., Infante, G., Élez, E., Fakih, M., Jayachandran, P., Shah, A. T., Salati, M., Fenocchio, E., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-003370 · Cited by 25 · see citing works
Self-citationMalignant Pleural Effusions—A Window Into Local Anti-Tumor T Cell Immunity?
Principe, N., Kidman, J., Lake, R., Lesterhuis, W., Nowak, A., McDonnell, A., & Chee, J. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.672747 · Cited by 24 · see citing works
Epaillard, N., Benítez, J. C., Gorría, T., et al. (2021) · Lung Cancer · doi:10.1016/j.lungcan.2021.03.015 · Cited by 21 · see citing works
Aarnink, A., Fumet, J.-D., Favier, L., Truntzer, C., & Ghiringhelli, F. (2020) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-020-03262-2 · Cited by 16 · see citing works
Pietrantonio, F., Barretta, F., Fanotto, V., et al. (2018) · Oncology · doi:10.1159/000491753 · Cited by 14 · see citing works
Self-citation(2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-iti11-1 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Borelli, B., Antoniotti, C., Carullo, M., Germani, M. M., Conca, V., & Masi, G. (2022) · Cancers · doi:10.3390/cancers14204974 · Cited by 62 · see citing works
Self-citationCurrent and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy
Nikolouzakis, T. K., Chrysos, E., Docea, A. O., Fragkiadaki, P., Souglakos, J., Tsiaoussis, J., & Tsatsakis, A. (2024) · Cancers · doi:10.3390/cancers16111995 · Cited by 37 · see citing works
- Authors
- Fucà, G., Cohen, R., Lonardi, S., Shitara, K., Elez, M. E., Fakih, M., Chao, J., Klempner, S. J., Emmett, M., Jayachandran, P., Bergamo, F., García, M. D., Mazzoli, G., Provenzano, L., Colle, R., Svrcek, M., Ambrosini, M., Randon, G., Shah, A. T., Salati, M., Fenocchio, E., Salvatore, L., Chida, K., Kawazoe, A., Conca, V., Curigliano, G., Corti, F., Cremolini, C., Overman, M., Andre, T., & Pietrantonio, F.
- Affiliations
- Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
- Inserm (FR)
- Istituto Oncologico Veneto (IT)
- National Cancer Center Hospital East (JP)
- Department of Medical Oncology, Vall d'Hebron Barcelona Hospital Campus, Vall d'Hebron Institute of Oncology (VHIO), Universitat Autonoma de Barcelona, Barcelona, Spain
- City Of Hope National Medical Center (US)
- Harvard University (US)
- University of Southern California (US)
- Universitat Autònoma de Barcelona (ES)
- Sorbonne Université, Department of Medical Oncology, Hôpital Saint-Antoine, AP-HP and INSERM, Unité Mixte de Recherche Scientifique 938, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancer, Equipe labellisée par la Ligue Nationale contre le Cancer, Paris, France
- Baylor College of Medicine (US)
- University of Modena and Reggio Emilia (IT)
- Candiolo Cancer Institute (IT)
- Agostino Gemelli University Polyclinic (IT)
- University of Pisa (IT)
- University of Milan (IT)
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Pietrantonio, Filippo
- ORCID
- Fucà, Giovanni
- Cohen, Romain
- Lonardi, Sara
- Shitara, Kohei
- Fakih, Marwan
- Chao, Joseph
- Klempner, Samuel J
- Emmett, Matthew
- Jayachandran, Priya
- Bergamo, Francesca
- Provenzano, Leonardo
- Svrcek, Magali
- Ambrosini, Margherita
- Randon, Giovanni
- Salati, Massimiliano
- Fenocchio, Elisabetta
- Salvatore, Lisa
- Chida, Keigo
- Kawazoe, Akihito
- Conca, Veronica
- Curigliano, Giuseppe
- Corti, Francesca
- Cremolini, Chiara
- Overman, Michael
- Andre, Thierry
- Pietrantonio, Filippo
- Venue
- Journal for ImmunoTherapy of Cancer
- Publisher
- BMJ
- Published
- 2022-02
- Volume
- 10
- Issue
- 2
- Pages
- e004001
- ISSN
- 2051-1426 (ISSN-L)
- PMC
- PMC8811606
- OpenAlex
- W4210300714
- Cited by
- 129
- References
- 33
- Citations by year
- 2026: 28 · 2025: 31 · 2024: 25 · 2023: 27 · 2022: 17 · 2012: 1
- FWCI
- 10.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal for ImmunoTherapy of Cancer (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by-nc)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion, cc-by-nc)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- PubliCatt (Università Cattolica del Sacro Cuore) (submittedVersion, other-oa)
- Funders
- Amgen
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Taiho Pharmaceutical
- MacroGenics
- Daiichi-Sankyo
- Eisai
- Astellas Pharma
- Servier
- Ono Pharmaceutical
- Chugai Pharmaceutical
- Foundation Medicine
- Daiichi Sankyo Europe
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Surgery › Intraperitoneal and Appendiceal Malignancies
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- ascites, peritoneal carcinomatosis, immune checkpoint inhibitors, immune resistance, mismatch repair deficiency, microsatellite instability-high, metastatic colorectal cancer, metastatic gastric cancer, anti-PD-1 therapy, PD-L1 inhibitors, anti-CTLA-4, prognostic factors, progression-free survival, overall survival, malignant effusions, immunosuppression, tumor microenvironment
- MeSH terms
- Immune Checkpoint Inhibitors, Aged, Ascites, Female, Humans, Male, Neoplasm Metastasis, Retrospective Studies, Stomach Neoplasms, Colorectal Neoplasms, Survival Analysis, Microsatellite Instability
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
