Table 1.

Summary of CRC study methodology

Author	Year	Design	colon or rectal	Use of chemotherapy	N	Open/laparoscopic/robotic	Outcome	NK cell studied	Functional analysis
Kim [19]	2016	RCTa	Both	Unreported	60	Lapb	Effect of opioids on NK cell function	Circulating	K562c LDHd release, circulating IL-2e
Kondo [11]	2003	Random prospective sampling	Colon	Unreported	140	Open	Correlation of pre-op NK cell function with stage and DFSf	Circulating	Cr releaseg K562
Pugh [13]	2014	Prospective cohort	Both	Unreported	11	Unreported	Distribution of T cells and NK cells in hepatic metastases	Tumoural and circulating	Flow cytometry
Espi [14]	1995	Prospective cohort	Both	Unreported	55	Open	Effect of curative intent surgery on NK cell cytocidal function	Circulating	Cr release K562
Furue [4]	2008	Case–control	Both	Unreported	379/1137 matched case/healthy controls	Unreported	NKG2D receptor haplotype (high or low activity)	Circulating	Direct sequencing of single nucleotide polymorphism
Tartter [1]	1987	Prospective cohort	Both	Unreported	102	Open	Prognostic influence of NK cell function	Circulating	Cr release K562
Wichmann [22]	2015	Prospective cohort	Both and benign	Unreported	70	Lap vs. open	Effect of lap vs. open surgery on IL-6, CRPh, NK count	Circulating	Flow cytometry and cytokine assay
Gharagozloo [5]	2015	Case–control	Both	Unreported	54 cancer 24 controls	Unreported	NKG2D receptor expression	Circulating	Flow cytometry
Halama [12]	2015	Prospective sample	Both	Unreported	112	Unreported	Tissue distribution of NK cells in primary CRC, CRC metastases and liver adenomas	Tumoural	IHCi to identify NK cells
Imai [8]	2000	Prospective cohort	All cancers	NA	3625	NA	11 year follow-up of patients after initial assessment of natural cytocidal activity of PBMCSj	Circulating	Cr release K562
Jobin [9]	2017	Prospective	Both	NA	872	NA	Peripheral NK cell activity as a screening test for CRC compared with colonoscopy	Circulating	IFNG release (whole blood + proprietary stimulatory cytokine mix)
Jung [10]	2018	Prospective	Both	NA	1818	NA	NK cell activity in screen population relating to CRC and adenoma	Circulating	IFNG release (whole blood + proprietary stimulatory cytokine mix)
Li Qiu [23]	2015	Retrospective review	Both	nil	1404	Unreported	Effect of perioperative blood transfusion on NK cells and prognosis	Circulating	Unclear
Santos [16]	2014	Prospective	Both	Unreported	30	Unreported	Relationship between circulating tumour cells and NK cells in metastatic colorectal cancer	Circulating	Cr release K562 and flow cytometry (FACS)
Wang [15]	2017	Prospective matched case control	both	Unreported	89: 47 rectal, 42 colon + healthy volunteers	Unreported	NK cell number and Tim-3 expression	Circulating	Flow cytometry
Zhu [33]	2013	Retrospective review	Both (59 colon, 36 rectal)	Adjuvant ± neoadjuvant chemotherapy	96 (21 in intervention)	Unreported	Effect of adjuvant cytokine induced killer cell infusion on DFS	NA	NA
Ross [29]	2009	RCT	Both	Mixed	78; 45 intervention 33 control	Unreported	Effect of nurse led home psychosocial support on immune function	Circulating	Cr release K562
Xu [38]	2011	Case–control ex vivo	Both (59 rectal)	None	119 case 101 control	Pre-operative	Difference in immune cell gene expression in CRC vs. control	Circulating	RNA gene expression DNA microarray and gene tubes
Radice [39]	2014	Cohort ex vivo	Both	None	25	Pre-operative	Effect of IFNG and SKA (sequential kinetic activation)-IFNG on CRC NK cell function	Circulating	Cr release K562 and CRC cell line
McGilvray [7]	2009	Lab human	Both	Unreported	462	Unreported	NKG2D ligand expression	Circulating	Flow cytometry

^a Randomised control trial

^b laparoscopic

^c K562 myeloid cell line

^d Lactate dehydrogenase

^e Interleukin 2

^f Disease free survival

^g Chromium release assay

^h C-reactive protein

ⁱ Immunohistochemistry

^j Peripheral Blood Mononuclear Cells