Journal of Immunology Research

Review Article

T Cells and Adoptive Immunotherapy: Recent Developments and Future Prospects in Gastrointestinal Oncology

Table 1

Studies correlating colorectal cancer patient survival with TIL subsets.


N° of events				High density of T-cells (versus low density)				References
Sample size	OS	CS	Disease stage	T-cell subset analysed	5-year CS, OS, or DFS, long-rank value	CS, OS, or DFS univariate HR (95% Cl)*, value	CS, OS, or DFS multivariate HR (95% Cl)*, value	References

131	—	—	Dukes’ A–D	CD8⁺	(OS)	—	0.61 (0.41–0,89)	[139]; 58: 3491–3494

				CD3⁺	(OS)	—	(OS) 0.40 (0.19–0.85) (OS)
109	37	—	II-III	CD8⁺	(OS)	—	0.33 (0.15–0.73) (OS)	[140]; 159: 297–304
				GZMB⁺	(OS)	—	0.23 (0.10–0.50) (OS)

				CD8⁺	77% (versus 38%) (CS)	—	—
93	59	47	Dukes’ C	CD45RO⁺	66% (versus 33%) (CS)	—	—	[141]; 17: 25–29
				CD68⁺	60% (versus 37%) (CS)	—	—

72	—	—	I–IV	CD134⁺	(CS)	—	—	[142]; 183: 512–518

41	25	—	Dukes’ A–D	CD4⁺/CD8⁺ ratio	22% (versus 61%) (OS)	—	(OS)	[143]; 52: 423–428

97	—	—	—	CD8⁺	—	(OS)	—	[144]; 10: 309–313.

152	—	—	III	CD8⁺	(CS)	—	—	[145]; 35:808–816

93	—	—	II-III	CD8⁺	(DFS)	—	0.56 (0.32–0.99) (DFS)	[146]; 84: 493–501

371	—	74	I–IV	CD8⁺	(CS)	—	0.43 (0.23–0.83) (CS)	[147]; 91: 1711–1717

336	158	—	Dukes’ A–D	CD45RO⁺	65% (versus 35%) (OS) 72% (versus 50%) (DFS)	—	(OS)	[148]; 353: 2654–2666

				CD3⁺	(CS)	—	—
117	—	—	Dukes’ A–D	CD8⁺	(CS)	—	—	[149]; 4: 1351–1357
				CD16⁺	(CS)	—	—

				CD3⁺	73% (versus 40%) (OS) 81% (versus 54%) (DFS)	—	0.53 (0.40–0.70) (OS) 0.42 (0.29–0.60) (DFS)
				CD8⁺	72% (versus 50%) (OS)	—	—
406	—	—	I–III	CD45RO⁺	82% (versus 56%) (DFS) 68% (versus 33%) (OS)	—	—	[150]; 313: 1960–1964
				GZMB⁺	77% (versus 37%) (DFS) 72% (versus 61%) (OS)	—	—
				CD3⁺, CD45RO⁺	84% (versus 68%) (DFS) (DFS)	—	—

587	—	—	I-II (MSS only)	CD8⁺	—	0.47 (0.33 0.68) (CS)	0.47 (0.30–0.73) (CS)	[151]; 112: 495–502

392	—	226	I-II (Rectum only)	CD8⁺	—	0.55 (0.41–0.74) (CS)	0.63 (0.45–0.88) (CS)	[152]; 99: 1712–1717

101	—	—	II-III	CD3⁺/FOXP3⁺ ratio	71% (versus 62%) (OS) 67% (versus 46%) (DFS)	0.57 (0.30–1.09) (OS) 0.46 (0.24–0.90) (DFS)	0.47 (0.24–0.94) (DFS)	[153]; 137: 1270–1279

					Node-negative (CS)
286	—	136	II-III	CD3⁺	Node-positive (CS)	—	—	[154]; 10: 877–884
					Node-negative (DFS)
					Node-positive (DFS)

					MSS group 162% (versus 46%) (CS)	—	0.73 (0.60–0.90) (CS)
1232	—	—	I-III	FOXP3⁺	MSS group 2 (CS) 60% (versus 44%) (CS)	—	0.70 (0.60–0.90) (CS)	[155]; 126: 2635–2643
					MSI group (CS) 75%? (versus 63%?) (CS)	—	0.63 (0.3–1.2) (CS)

				CD8⁺	—	0.74 (0.67–0.82) (CS)	NS (CS)
445	—	—	II-III	CD45RO⁺	—	0.74 (0.65–0.84) (CS)	NS (CS)	[156]; 27: 186–192
				FOXP3⁺	—	0.78 (0.70–0.87) (CS)	0.54 (0.38–0.77) (CS)

				CD8⁺	(OS and DFS)	—	—
411	—	—	I-II	CD45RO⁺	(OS and DFS)	—	—	[157]; 27: 5944–5951
				CD8⁺ plus CD45RO⁺	(OS and DFS)	—	(CS, OS and DFS)

				CD3⁺	(OS)	—	0.54 (0.18–1.59) (OS)
209	100	100	I–IV	CD8⁺	(OS)	—	2.06 (0.67–6.39) (OS)	[158]; 11: 19
				GZMB⁺	—	—	1.18 (0.45–3.13) (OS)

94	—	—	I–IV	CD8⁺/FOXP3⁺ ratio	(OS)	0.35 (0.15–0.81) (OS)	0.40 (0.17–0.94) (OS)	[159]; 59: 653–661

57	—	—	—	FOXP3⁺	—	(DFS) (OS)	—	[160]; 33: 435–441

				CD3⁺	0.010 (DFS) 0.061 (OS)	0.003 (DFS) 0.039 (OS)	0.20 (0.02–2.60) 0.22 (DFS)
87	—	—	II	CD25⁺	0.013 (DFS) 0.15 (OS)	0.002 (DFS) 0.017 (OS)	0.22 (0.02–2.35) 0.21 (DFS)	[161]; 116:5188–5199
				CD45RO⁺	0.049 (DFS) 0.16 (OS)	0.014 (DFS) 0.037 (OS)	0.24 (0.02–1.10) 0.014 (DFS)
				FOXP3⁺	0.009 (DFS) 0.027 (OS)	0.005 (DFS) 0.040 (OS)	0.14 (0.07–0.85) 0.027 (DFS)

				CD3⁺	79% (versus 75%) Q4 (versus Q1)^† 0.19 (CS)	0.73 (0.49–1.08) Q4 (versus Q1)^† 0.070^‡ (CS)	1.30 (0.81–2.07) Q4 (versus Q1)^† 0.16^‡ (CS)
768	366	229	I-IV	CD8⁺	78% (versus 66%) Q4 (versus Q1)^† 0.026 (CS)	0.61 (0.42–0.88) Q4 (versus Q1)^† 0.007^‡ (CS)	0.81 (0.52–1.27) Q4 (versus Q1)^† 0.34^‡ (CS)	[162]; 222: 350–366
				CD45RO⁺	83% (versus 68%) Q4 (versus Q1)^† 0.0001 (CS)	0.40 (0.26–0.60) Q4 (versus Q1)^† 0.0001^‡ (CS)	0.51 (0.32–0.80) Q4 (versus Q1)^† ^‡ (CS)
				FOXP3⁺	80% (versus 64%) Q4 (versus Q1)^† 0.0001 (CS)	0.48 (0.32–0.70) Q4 (versus Q1)^† 0.0001^‡ (CS)	0.89 (0.59–1.34) Q4 (versus Q1)^† ^‡ (CS)

*HR is based on comparing high versus low score of a given T-cell subset. ^†Quartile of density (Q1-4, first to fourth quartile). ^‡P for trend. Cl: confidence interval; CS: colorectal cancer-specific survival; DFS: disease-free survival; HR: hazard ratio; MSI: microsatellite instability; NS: not significant; OS: overall survival.