Interrogating the interplay of angiogenesis and immunity in metastatic colorectal cancer

Table 1 Factors related to angiogenesis and immunity and studied as biomarkers in colorectal cancer

Factor	Biologic material	Pathway	Significance	Ref.
VEGF	Tissue, blood	Angiogenesis	Prognostic & predictive	Bendardaf et al[63] 2017, Des Guetz et al[7] 2006, Ferroni et al[64] 2006, Pascual et al[65] 2018, Tsai et al[66] 2013, Tsai et al[67] 2015, Boussios et al[68] 2019, Zygoń et al[23] 2017, Mohamed et al[69] 2019
VEGF polymorphism	Tissue, blood	Angiogenesis	Prognostic & predictive	Mousa et al[9] 2015
HIF-1α	Tissue	Angiogenesis	Prognostic	Baba et al[5] 2010
CTCs	Blood	Angiogenesis	Prognostic & predictive	Arrazubi et al[34] 2019, Burz et al[25] 2018, Cabel et al[28] 2017, Tan et al[33] 2018, Wang et al[35] 2019, Zhang et al[70] 2017
CTCs	Blood	Angiogenesis	Predictive	Nakamura et al[3] 2018
MicroRNA	Tissue, blood, stools	Angiogenesis	Prognostic & predictive	Balacescu et al[40] 2018, Boussios et al[68] 2019, Peng et al[41] 2017, To et al[38] 2018
MVD	Tissue	Immunity	Prognostic	den Uil et al[71] 2019, Des Guetz et al[7] 2006, Mohammed et al[72] 2020, Zhu et al[19] 2017, Zygoń et al[23] 2017

VEGF: Vascular endothelial growth factor; HIF-1α: Hypoxia–inducible factor 1-alpha; CTCs: Circulating tumor cells; MVD: Microvascular density.

Table 2 Clinical trials related to antiangiogenic agent therapy and immunotherapy in colorectal cancer

Status	Study title	Drugs	Country
Recruiting	A study evaluating the efficacy and safety of multiple immunotherapy-based treatment combinations in patients with metastatic colorectal cancer (Morpheus-CRC)	Regorafenib, atezolizumab	United States
Recruiting	Study of chemotherapy combination with autologous cell	Bevacizumab, oxaliplatin, capecitabine; Biological component: PD1-T cells	China
Recruiting	Treatment of colorectal liver metastases with immunotherapy and bevacizumab	Atezolizumab, bevacizumab, oxaliplatin	Korea
Recruiting	Neoadjuvant treatment in rectal cancer with radiotherapy followed by atezolizumab and bevacizumab (TARZAN)	Atezolizumab, bevacizumab	Netherlands
Not yet recruiting	Chemotherapy and immunotherapy as treatment for MSS metastatic	Capecitabine, oxaliplatin, bevacizumab, pembrolizumab	France
Not yet recruiting	QL1101 in combination with JS001 in patients with pMMR/MSS refractory metastatic	Bevacizumab, tripleitriumab	China
Not yet recruiting	Comparison of sintilimab to XELOX	Sintilimab vs XELOX + bevacizumab	China

CRC: Colorectal cancer; PD-1: Programmed cell death protein 1.