Prognostic implications of adaptive immune features in MMR-proficient colorectal liver metastases classified by histopathological growth patterns.
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
28
01
2021
accepted:
02
12
2021
revised:
24
10
2021
pubmed:
5
1
2022
medline:
29
4
2022
entrez:
4
1
2022
Statut:
ppublish
Résumé
After resection, colorectal cancer liver metastases (CRLM) surrounded by a desmoplastic rim carry a better prognosis than the metastases replacing the adjacent liver. However, these histopathological growth patterns (HGPs) are insufficient to guide clinical decision-making. We explored whether the adaptive immune features of HGPs could refine prognostication. From 276 metastases resected in 176 patients classified by HGPs, tissue microarrays were used to assess intratumoral T cells (CD3), antigen presentation capacity (MHC class I) and CD73 expression producing immunosuppressive adenosine. We tested correlations between these variables and patient outcomes. The 101 (57.4%) patients with dominant desmoplastic HGP had a median recurrence-free survival (RFS) of 17.1 months compared to 13.3 months in the 75 patients (42.6%) with dominant replacement HGP (p = 0.037). In desmoplastic CRLM, high vs. low CD73 was the only prognostically informative immune parameter and was associated with a median RFS of 12.3 months compared to 26.3, respectively (p = 0.010). Only in dominant replacement CRLM, we found a subgroup (n = 23) with high intratumoral MHC-I expression but poor CD3 Combining the assessments of HGP and adaptive immune features in resected CRLM could help identify patients at risk of early recurrence.
Sections du résumé
BACKGROUND
After resection, colorectal cancer liver metastases (CRLM) surrounded by a desmoplastic rim carry a better prognosis than the metastases replacing the adjacent liver. However, these histopathological growth patterns (HGPs) are insufficient to guide clinical decision-making. We explored whether the adaptive immune features of HGPs could refine prognostication.
METHODS
From 276 metastases resected in 176 patients classified by HGPs, tissue microarrays were used to assess intratumoral T cells (CD3), antigen presentation capacity (MHC class I) and CD73 expression producing immunosuppressive adenosine. We tested correlations between these variables and patient outcomes.
RESULTS
The 101 (57.4%) patients with dominant desmoplastic HGP had a median recurrence-free survival (RFS) of 17.1 months compared to 13.3 months in the 75 patients (42.6%) with dominant replacement HGP (p = 0.037). In desmoplastic CRLM, high vs. low CD73 was the only prognostically informative immune parameter and was associated with a median RFS of 12.3 months compared to 26.3, respectively (p = 0.010). Only in dominant replacement CRLM, we found a subgroup (n = 23) with high intratumoral MHC-I expression but poor CD3
CONCLUSIONS
Combining the assessments of HGP and adaptive immune features in resected CRLM could help identify patients at risk of early recurrence.
Identifiants
pubmed: 34980880
doi: 10.1038/s41416-021-01667-5
pii: 10.1038/s41416-021-01667-5
pmc: PMC9043179
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1329-1338Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
Références
Tomlinson JS, Jarnagin WR, DeMatteo RP, Fong Y, Kornprat P, Gonen M, et al. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007;25:4575–80.
doi: 10.1200/JCO.2007.11.0833
Buisman FE, Galjart B, van der Stok EP, Balachandran VP, Boerner T, Drebin JA, et al. Recurrence patterns after resection of colorectal liver metastasis are modified by perioperative systemic chemotherapy. World J Surg. 2020;44:876–86.
doi: 10.1007/s00268-019-05121-9
Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, et al. Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2013;14:1208–15.
doi: 10.1016/S1470-2045(13)70447-9
Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359:1350–5.
doi: 10.1126/science.aar4060
Van den Eynden GG, Majeed AW, Illemann M, Vermeulen PB, Bird NC, Hoyer-Hansen G, et al. The multifaceted role of the microenvironment in liver metastasis: biology and clinical implications. Cancer Res. 2013;73:2031–43.
doi: 10.1158/0008-5472.CAN-12-3931
Vermeulen PB, Colpaert C, Salgado R, Royers R, Hellemans H, Van Den Heuvel E, et al. Liver metastases from colorectal adenocarcinomas grow in three patterns with different angiogenesis and desmoplasia. J Pathol. 2001;195:336–42.
doi: 10.1002/path.966
van Dam PJ, van der Stok EP, Teuwen LA, Van den Eynden GG, Illemann M, Frentzas S, et al. International consensus guidelines for scoring the histopathological growth patterns of liver metastasis. Br J Cancer. 2017;117:1427–41.
doi: 10.1038/bjc.2017.334
Fernandez Moro C, Bozoky B, Gerling M. Growth patterns of colorectal cancer liver metastases and their impact on prognosis: a systematic review. BMJ Open Gastroenterol. 2018;5:e000217.
doi: 10.1136/bmjgast-2018-000217
Galjart B, Nierop PMH, van der Stok EP, van den Braak R, Hoppener DJ, Daelemans S, et al. Angiogenic desmoplastic histopathological growth pattern as a prognostic marker of good outcome in patients with colorectal liver metastases. Angiogenesis. 2019;22:355–68.
doi: 10.1007/s10456-019-09661-5
Höppener DJ, Galjart B, Nierop PMH, Buisman FE, van der Stok EP, Coebergh van den Braak RRJ, et al. Histopathological growth patterns and survival after resection of colorectal liver metastasis: an external validation study. JNCI Cancer Spectrum. 2021. https://doi.org/10.1093/jncics/pkab026 .
Katz SC, Bamboat ZM, Maker AV, Shia J, Pillarisetty VG, Yopp AC, et al. Regulatory T cell infiltration predicts outcome following resection of colorectal cancer liver metastases. Ann Surg Oncol. 2013;20:946–55.
doi: 10.1245/s10434-012-2668-9
Katz SC, Pillarisetty V, Bamboat ZM, Shia J, Hedvat C, Gonen M, et al. T cell infiltrate predicts long-term survival following resection of colorectal cancer liver metastases. Ann Surg Oncol. 2009;16:2524–30.
doi: 10.1245/s10434-009-0585-3
Halama N, Michel S, Kloor M, Zoernig I, Benner A, Spille A, et al. Localization and density of immune cells in the invasive margin of human colorectal cancer liver metastases are prognostic for response to chemotherapy. Cancer Res. 2011;71:5670–7.
doi: 10.1158/0008-5472.CAN-11-0268
Meshcheryakova A, Tamandl D, Bajna E, Stift J, Mittlboeck M, Svoboda M, et al. B cells and ectopic follicular structures: novel players in anti-tumor programming with prognostic power for patients with metastatic colorectal cancer. PLoS ONE. 2014;9:e99008.
doi: 10.1371/journal.pone.0099008
Mlecnik B, Van den Eynde M, Bindea G, Church SE, Vasaturo A, Fredriksen T, et al. Comprehensive intrametastatic immune quantification and major impact of immunoscore on survival. J Natl Cancer Inst. 2018. https://doi.org/10.1093/jnci/djx123 .
V Van den Eynde M, Mlecnik B, Bindea G, Fredriksen T, Church SE, Lafontaine L, et al. The link between the multiverse of immune microenvironments in metastases and the survival of colorectal cancer patients. Cancer Cell. 2018;34:1012.e3–26.e3.
doi: 10.1016/j.ccell.2018.11.003
Baldin P, Van den Eynde M, Mlecnik B, Bindea G, Beniuga G, Carrasco J, et al. Prognostic assessment of resected colorectal liver metastases integrating pathological features, RAS mutation and Immunoscore. J Pathol Clin Res. 2021;7:27–41.
doi: 10.1002/cjp2.178
Frentzas S, Simoneau E, Bridgeman VL, Vermeulen PB, Foo S, Kostaras E, et al. Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases. Nat Med. 2016;22:1294–302.
doi: 10.1038/nm.4197
Stremitzer S, Vermeulen P, Graver S, Kockx M, Dirix L, Yang D, et al. Immune phenotype and histopathological growth pattern in patients with colorectal liver metastases. Br J Cancer. 2020;122:1518–24.
doi: 10.1038/s41416-020-0812-z
Allard D, Chrobak P, Allard B, Messaoudi N, Stagg J. Targeting the CD73-adenosine axis in immuno-oncology. Immunol Lett. 2019;205:31–9.
doi: 10.1016/j.imlet.2018.05.001
Hoppener DJ, Nierop PMH, Hof J, Sideras K, Zhou G, Visser L, et al. Enrichment of the tumour immune microenvironment in patients with desmoplastic colorectal liver metastasis. Br J Cancer. 2020;123:196–206.
doi: 10.1038/s41416-020-0881-z
Anderson P, Aptsiauri N, Ruiz-Cabello F, Garrido F. HLA class I loss in colorectal cancer: implications for immune escape and immunotherapy. Cell Mol Immunol. 2021;18:556–65.
doi: 10.1038/s41423-021-00634-7
Turcotte S, Katz SC, Shia J, Jarnagin WR, Kingham TP, Allen PJ, et al. Tumor MHC class I expression improves the prognostic value of T-cell density in resected colorectal liver metastases. Cancer Immunol Res. 2014;2:530–7.
doi: 10.1158/2326-6066.CIR-13-0180
DePeaux, K & Delgoffe, GM Metabolic barriers to cancer immunotherapy. Nat Rev Immunol. 2021. https://doi.org/10.1038/s41577-021-00541-y .
Messaoudi N, Cousineau I, Arslanian E, Henault D, Stephen D, Vandenbroucke-Menu F, et al. Prognostic value of CD73 expression in resected colorectal cancer liver metastasis. Oncoimmunology. 2020;9:1746138.
doi: 10.1080/2162402X.2020.1746138
Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg. 1999;230:309–18.
doi: 10.1097/00000658-199909000-00004
Halama N, Spille A, Lerchl T, Brand K, Herpel E, Welte S, et al. Hepatic metastases of colorectal cancer are rather homogeneous but differ from primary lesions in terms of immune cell infiltration. Oncoimmunology. 2013;2:e24116.
doi: 10.4161/onci.24116
Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313:1960–4.
doi: 10.1126/science.1129139
Mlecnik B, Bindea G, Kirilovsky A, Angell HK, Obenauf AC, Tosolini M, et al. The tumor microenvironment and Immunoscore are critical determinants of dissemination to distant metastasis. Sci Transl Med. 2016;8:327ra26.
doi: 10.1126/scitranslmed.aad6352
Kirilovsky A, Marliot F, El Sissy C, Haicheur N, Galon J, Pages F. Rational bases for the use of the Immunoscore in routine clinical settings as a prognostic and predictive biomarker in cancer patients. Int Immunol. 2016;28:373–82.
doi: 10.1093/intimm/dxw021
Feise RJ. Do multiple outcome measures require p-value adjustment? BMC Med Res Methodol. 2002;2:8.
doi: 10.1186/1471-2288-2-8
Rothman KJ. No adjustments are needed for multiple comparisons. Epidemiology. 1990;1:43–6.
doi: 10.1097/00001648-199001000-00010
Streiner DL, Norman GR. Correction for multiple testing: is there a resolution? Chest. 2011;140:16–8.
doi: 10.1378/chest.11-0523
Rubbia-Brandt L, Giostra E, Brezault C, Roth AD, Andres A, Audard V, et al. Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery. Ann Oncol. 2007;18:299–304.
doi: 10.1093/annonc/mdl386
Tanis E, Julie C, Emile JF, Mauer M, Nordlinger B, Aust D, et al. Prognostic impact of immune response in resectable colorectal liver metastases treated by surgery alone or surgery with perioperative FOLFOX in the randomised EORTC study 40983. Eur J Cancer. 2015;51:2708–17.
doi: 10.1016/j.ejca.2015.08.014
Palmieri V, Lazaris A, Mayer TZ, Petrillo SK, Alamri H, Rada M, et al. Neutrophils expressing lysyl oxidase-like 4 protein are present in colorectal cancer liver metastases resistant to anti-angiogenic therapy. J Pathol. 2020;251:213–23.
doi: 10.1002/path.5449