Table 3.

Joint effect of localization and BOR on TIL score and percentage of CD3⁺, CD8⁺, and CTLA-4⁺ TILs

Variables		TIL score			CD3 TIL %			CD8+ TIL %			CTLA4+ TIL %
BOR	TIL localization	GMR	95% CL	P value	GMR	95% CL	P value	GMR	95% CI	P value	GMR	95% CL	P value
R	TILTC	1.00	(Ref.)	< 0.001	1.00	(Ref.)	< 0.001	1.00	(Ref.)	< 0.001	1.00	(Ref.)	< 0.001
	TILIM	1.75	1.44–2.14		4.02	2.01–8.04		3.19	1.74–5.84		3.98	2.04–7.75
NR	TILTC	0.56	0.39–0.86		0.38	0.10–1.49		0.33	0.09–1.20		0.15	0.04–0.51
	TILIM	1.01	0.65–1.58		1.53	0.32–7.04		1.07	0.26–4.39		0.58	0.14–2.38

TIL score and percentages of CD3⁺, CD8⁺, and CTLA-4⁺ TILs were evaluated in responding (R) and non-responding (NR) patients, in relation to the two cellular localizations of invasive margin (IM) and tumor center (TC), by histological and immunohistochemical staining of formalin-fixed, paraffin-embedded melanoma tissue sections, as described in the section “Materials and methods”. Results were evaluated as geometric mean ratio (GMR), i.e., the ratio between the geometric mean (GM) of R patients and GM of NR patients. All GMRs were adjusted for age at IPI, sex, number of brain metastases, time of IPI therapy, and number of pre-IPI therapies. Statistical significance: 0.05

TIL tumor infiltrating lymphocytes, TIL^TC TIL at the TC, TIL^IM TIL at the IM, 95% CL 95% confidence limits for GMR, R responding patients (irCR + irPR + irSD), NR non-responding patients (irPD), Ref. reference category (i.e., GM level in the R patients and TIL^TC localization), P value probability level of significance tests