{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:50:21Z","timestamp":1792785021222,"version":"4.5.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T00:00:00Z","timestamp":1754697600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T00:00:00Z","timestamp":1754697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"the National High Level Hospital Clinical Research Funding","award":["No. 2022CR65"],"award-info":[{"award-number":["No. 2022CR65"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-13701-0","type":"journal-article","created":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T08:33:48Z","timestamp":1754728428000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Real world effectiveness of chemotherapy plus bevacizumab with immunotherapy in colorectal cancer"],"prefix":"10.1038","volume":"15","author":[{"given":"Zhao","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shikai","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,9]]},"reference":[{"issue":"3","key":"13701_CR1","first-page":"229","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray, F. et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 74(3), 229\u2013263 (2024).","journal-title":"CA Cancer J. Clin."},{"issue":"10207","key":"13701_CR2","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1016\/S0140-6736(19)32319-0","volume":"394","author":"E Dekker","year":"2019","unstructured":"Dekker, E. et al. Colorectal cancer. Lancet 394(10207), 1467\u20131480 (2019).","journal-title":"Lancet"},{"issue":"7","key":"13701_CR3","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1001\/jama.2021.0106","volume":"325","author":"LH Biller","year":"2021","unstructured":"Biller, L. H. & Schrag, D. Diagnosis and treatment of metastatic colorectal cancer: A review. JAMA 325(7), 669\u2013685 (2021).","journal-title":"JAMA"},{"issue":"8","key":"13701_CR4","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1038\/s41590-023-01574-2","volume":"24","author":"FR Carbone","year":"2023","unstructured":"Carbone, F. R. & Mackay, L. K. Functional T cell tolerance by peripheral tissue-based checkpoint control. Nat. Immunol. 24(8), 1224\u20131225 (2023).","journal-title":"Nat. Immunol."},{"issue":"9","key":"13701_CR5","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1158\/2159-8290.CD-18-0367","volume":"8","author":"SC Wei","year":"2018","unstructured":"Wei, S. C., Duffy, C. R. & Allison, J. P. Fundamental mechanisms of immune checkpoint blockade therapy. Cancer Discov. 8(9), 1069\u20131086 (2018).","journal-title":"Cancer Discov."},{"issue":"7","key":"13701_CR6","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1016\/S1470-2045(22)00290-X","volume":"23","author":"RJ Motzer","year":"2022","unstructured":"Motzer, R. J. et al. Nivolumab plus cabozantinib versus sunitinib in first-line treatment for advanced renal cell carcinoma (CheckMate 9ER): Long-term follow-up results from an open-label, randomised, phase 3 trial. Lancet Oncol. 23(7), 888\u2013898 (2022).","journal-title":"Lancet Oncol."},{"issue":"9","key":"13701_CR7","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1016\/j.annonc.2022.05.519","volume":"33","author":"M Maio","year":"2022","unstructured":"Maio, M. et al. Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: Updated analysis from the phase II KEYNOTE-158 study. Ann. Oncol. 33(9), 929\u2013938 (2022).","journal-title":"Ann. Oncol."},{"issue":"1","key":"13701_CR8","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.immuni.2019.12.011","volume":"52","author":"PS Hegde","year":"2020","unstructured":"Hegde, P. S. & Chen, D. S. Top 10 challenges in cancer immunotherapy. Immunity 52(1), 17\u201335 (2020).","journal-title":"Immunity"},{"issue":"17","key":"13701_CR9","doi-asserted-by":"publisher","first-page":"4680","DOI":"10.1158\/1078-0432.CCR-21-0557","volume":"27","author":"SJ Casak","year":"2021","unstructured":"Casak, S. J. et al. FDA approval summary: Pembrolizumab for the first-line treatment of patients with MSI-H\/dMMR advanced unresectable or metastatic colorectal carcinoma. Clin. Cancer Res. 27(17), 4680\u20134684 (2021).","journal-title":"Clin. Cancer Res."},{"issue":"4","key":"13701_CR10","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1038\/s41568-023-00660-9","volume":"24","author":"S Yuan","year":"2024","unstructured":"Yuan, S., Almagro, J. & Fuchs, E. Beyond genetics: Driving cancer with the tumour microenvironment behind the wheel. Nat. Rev. Cancer 24(4), 274\u2013286 (2024).","journal-title":"Nat. Rev. Cancer"},{"key":"13701_CR11","doi-asserted-by":"publisher","first-page":"1291530","DOI":"10.3389\/fimmu.2023.1291530","volume":"14","author":"C Qian","year":"2023","unstructured":"Qian, C. et al. Targeting vascular normalization: A promising strategy to improve immune-vascular crosstalk in cancer immunotherapy. Front. Immunol. 14, 1291530 (2023).","journal-title":"Front. Immunol."},{"key":"13701_CR12","doi-asserted-by":"crossref","unstructured":"Lenz, H. J., Parikh, A., Spigel, D. R., et al. Modified FOLFOX6 plus bevacizumab with and without nivolumab for first-line treatment of metastatic colorectal cancer: Phase 2 results from the CheckMate 9X8 randomized clinical trial. J. Immunother. Cancer, 12(3), (2024).","DOI":"10.1136\/jitc-2023-008409"},{"issue":"2","key":"13701_CR13","first-page":"183","volume":"23","author":"EX Chen","year":"2024","unstructured":"Chen, E. X. et al. Pembrolizumab plus binimetinib with or without chemotherapy for MSS\/pMMR metastatic colorectal cancer: Outcomes from KEYNOTE-651 cohorts A, C, and E. Clin. Colorectal Cancer 23(2), 183\u2013193 (2024).","journal-title":"Clin. Colorectal Cancer"},{"issue":"6","key":"13701_CR14","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1016\/S1470-2045(19)30027-0","volume":"20","author":"C Eng","year":"2019","unstructured":"Eng, C. et al. Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): A multicentre, open-label, phase 3, randomised, controlled trial. Lancet Oncol. 20(6), 849\u2013861 (2019).","journal-title":"Lancet Oncol."},{"key":"13701_CR15","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2023.101917","volume":"58","author":"M Fakih","year":"2023","unstructured":"Fakih, M. et al. Regorafenib plus nivolumab in patients with mismatch repair-proficient\/microsatellite stable metastatic colorectal cancer: A single-arm, open-label, multicentre phase 2 study. EClinicalMedicine 58, 101917 (2023).","journal-title":"EClinicalMedicine"},{"issue":"4_suppl","key":"13701_CR16","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1200\/JCO.2025.43.4_suppl.23","volume":"43","author":"M Fakih","year":"2025","unstructured":"Fakih, M. et al. Preliminary results from a randomized, open-label, phase 2 study of botensilimab (BOT) with or without balstilimab (BAL) in refractory microsatellite stable metastatic colorectal cancer with no liver metastases (MSS mCRC NLM). J. Clin. Oncol. 43(4_suppl), 23 (2025).","journal-title":"J. Clin. Oncol."},{"key":"13701_CR17","doi-asserted-by":"crossref","unstructured":"Segal, N. H., Passhak, M., K\u00f6se, F., et al. Co-formulated favezelimab plus pembrolizumab versus standard-of-care in previously treated, PD-L1-positive metastatic colorectal cancer: The phase 3, randomized KEYFORM-007 study. J. Clin. Oncol. 43(4_suppl): LBA248-LBA (2025).","DOI":"10.1200\/JCO.2025.43.4_suppl.LBA248"},{"issue":"4","key":"13701_CR18","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1038\/s41591-024-02813-1","volume":"30","author":"F Wang","year":"2024","unstructured":"Wang, F. et al. Combined anti-PD-1, HDAC inhibitor and anti-VEGF for MSS\/pMMR colorectal cancer: a randomized phase 2 trial. Nat Med 30(4), 1035\u20131043 (2024).","journal-title":"Nat Med"},{"issue":"6","key":"13701_CR19","doi-asserted-by":"publisher","first-page":"5075","DOI":"10.1021\/acs.jmedchem.4c00250","volume":"67","author":"H Wang","year":"2024","unstructured":"Wang, H. et al. Subtle structural changes across the boundary between A(2A)R\/A(2B)R dual antagonism and A(2B)R antagonism: A novel class of 2-aminopyrimidine-based derivatives. J. Med. Chem. 67(6), 5075\u20135092 (2024).","journal-title":"J. Med. Chem."},{"issue":"2","key":"13701_CR20","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1038\/s41591-022-02181-8","volume":"29","author":"J Tian","year":"2023","unstructured":"Tian, J. et al. Combined PD-1, BRAF and MEK inhibition in BRAF(V600E) colorectal cancer: A phase 2 trial. Nat. Med. 29(2), 458\u2013466 (2023).","journal-title":"Nat. Med."},{"key":"13701_CR21","doi-asserted-by":"publisher","unstructured":"Antoniotti C. et al. Upfront Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan Plus Bevacizumab With or Without Atezolizumab for Patients With Metastatic Colorectal Cancer: Updated and Overall Survival Results of the ATEZOTRIBE Study[J]. J  Clinic Oncol: Official J Amer Soc Clinic Oncol. 42(22), 2637\u20132644. https:\/\/doi.org\/10.1200\/JCO.23.02728.","DOI":"10.1200\/JCO.23.02728"},{"issue":"7","key":"13701_CR22","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1016\/j.ccell.2024.06.009","volume":"42","author":"Y Chen","year":"2024","unstructured":"Chen, Y. et al. Spatiotemporal single-cell analysis decodes cellular dynamics underlying different responses to immunotherapy in colorectal cancer. Cancer Cell 42(7), 1268\u201385.e7 (2024).","journal-title":"Cancer Cell"},{"issue":"5","key":"13701_CR23","doi-asserted-by":"publisher","first-page":"351","DOI":"10.4132\/jptm.2020.05.15","volume":"54","author":"JM Bae","year":"2020","unstructured":"Bae, J. M. et al. Immune landscape and biomarkers for immuno-oncology in colorectal cancers. J. Pathol. Transl. Med. 54(5), 351\u2013360 (2020).","journal-title":"J. Pathol. Transl. Med."},{"key":"13701_CR24","doi-asserted-by":"crossref","unstructured":"Sugimura-Nagata, A., Koshino, A., Inoue, S., et al. Expression and prognostic significance of CD47-SIRPA macrophage checkpoint molecules in colorectal cancer. Int. J. Mol. Sci., 22(5), (2021).","DOI":"10.3390\/ijms22052690"},{"issue":"4","key":"13701_CR25","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1159\/000496027","volume":"86","author":"R Fujiwara-Tani","year":"2019","unstructured":"Fujiwara-Tani, R. et al. Concurrent expression of CD47 and CD44 in colorectal cancer promotes malignancy. Pathobiology 86(4), 182\u2013189 (2019).","journal-title":"Pathobiology"},{"key":"13701_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2025.118014","volume":"186","author":"A Rahimi","year":"2025","unstructured":"Rahimi, A. et al. Combination therapy with immune checkpoint inhibitors in colorectal cancer: Challenges, resistance mechanisms, and the role of microbiota. Biomed. Pharmacother. 186, 118014 (2025).","journal-title":"Biomed. Pharmacother."},{"key":"13701_CR27","doi-asserted-by":"crossref","unstructured":"Yuan J, Zhao X, Li Y, et al. The Association between blood indexes and immune cell concentrations in the primary tumor microenvironment predicting survival of immunotherapy in gastric cancer. Cancers (Basel), 14(15), (2022).","DOI":"10.3390\/cancers14153608"},{"issue":"3","key":"13701_CR28","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1007\/s10120-019-01027-6","volume":"23","author":"Z Li","year":"2020","unstructured":"Li, Z. et al. The clinical value and usage of inflammatory and nutritional markers in survival prediction for gastric cancer patients with neoadjuvant chemotherapy and D2 lymphadenectomy. Gastric Cancer 23(3), 540\u2013549 (2020).","journal-title":"Gastric Cancer"},{"issue":"36","key":"13701_CR29","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000030380","volume":"101","author":"W Cao","year":"2022","unstructured":"Cao, W. et al. Prognostic significance of systemic immune-inflammation index in patients with bladder cancer: A systematic review and meta-analysis. Medicine (Baltimore) 101(36), e30380 (2022).","journal-title":"Medicine (Baltimore)"},{"issue":"4","key":"13701_CR30","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1007\/s11523-021-00819-0","volume":"16","author":"G Fuc\u00e0","year":"2021","unstructured":"Fuc\u00e0, G. et al. The pan-immune-inflammation value in patients with metastatic melanoma receiving first-line therapy. Target Oncol. 16(4), 529\u201336 (2021).","journal-title":"Target Oncol."},{"key":"13701_CR31","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.724443","volume":"12","author":"R Zeng","year":"2021","unstructured":"Zeng, R. et al. PIV and PILE score at baseline predict clinical outcome of anti-PD-1\/PD-L1 inhibitor combined with chemotherapy in extensive-stage small cell lung cancer patients. Front. Immunol. 12, 724443 (2021).","journal-title":"Front. Immunol."},{"issue":"1","key":"13701_CR32","doi-asserted-by":"publisher","first-page":"14662","DOI":"10.1038\/s41598-021-94184-7","volume":"11","author":"AB \u015eahin","year":"2021","unstructured":"\u015eahin, A. B. et al. Low pan-immune-inflammation-value predicts better chemotherapy response and survival in breast cancer patients treated with neoadjuvant chemotherapy. Sci. Rep. 11(1), 14662 (2021).","journal-title":"Sci. Rep."},{"key":"13701_CR33","doi-asserted-by":"crossref","unstructured":"Ligorio F, Fuc\u00e0 G, Zattarin E, et al. The pan-immune-inflammation-value predicts the survival of patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer treated with first-line Taxane-Trastuzumab-Pertuzumab. Cancers (Basel), 13(8) (2021).","DOI":"10.3390\/cancers13081964"},{"issue":"12","key":"13701_CR34","doi-asserted-by":"publisher","first-page":"2272","DOI":"10.1136\/gutjnl-2023-329543","volume":"72","author":"W Fong","year":"2023","unstructured":"Fong, W. et al. Lactobacillus gallinarum-derived metabolites boost anti-PD1 efficacy in colorectal cancer by inhibiting regulatory T cells through modulating IDO1\/Kyn\/AHR axis. Gut 72(12), 2272\u20132285 (2023).","journal-title":"Gut"},{"issue":"6","key":"13701_CR35","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/nm.4086","volume":"22","author":"T Saito","year":"2016","unstructured":"Saito, T. et al. Two FOXP3(+)CD4(+) T cell subpopulations distinctly control the prognosis of colorectal cancers. Nat. Med. 22(6), 679\u2013684 (2016).","journal-title":"Nat. Med."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-13701-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-13701-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-13701-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T18:27:40Z","timestamp":1757356060000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-13701-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,9]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["13701"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-13701-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,9]]},"assertion":[{"value":"18 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This study has been approved by the Ethics Committee of the Peking University First Hospital and Jilin Cancer Hospital.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}],"article-number":"29170"}}