Emerging dynamics pathways of response and resistance to PD-1 and CTLA-4 blockade: tackling uncertainty by confronting complexity

Relecom, Allan; Merhi, Maysaloun; Inchakalody, Varghese; Uddin, Shahab; Rinchai, Darawan; Bedognetti, Davide; Dermime, Said

doi:10.1186/s13046-021-01872-3

Journal of Experimental & Clinical Cancer Research

Table 1 Dynamic immune correlates of anti-CTLA-4 and anti-PD-1 treatment outcome in clinical studies

From: Emerging dynamics pathways of response and resistance to PD-1 and CTLA-4 blockade: tackling uncertainty by confronting complexity

Dynamic biomarkers	Associated outcome	Cancer type	ICI treatment	References
Expansion and activation of CD8 + effector T cell in the tumor	Clinical benefit	Melanoma	Anti-CTLA-4 monotherapy	[24, 25]
	Clinical benefit	Melanoma	Anti-PD-1 monotherapy	[95,96,97]
Increase in absolute lymphocyte count in the periphery	Clinical benefit	Melanoma	Anti-CTLA-4 monotherapy	[53,54,55,56]
Expansion in CD8 + memory T cells in the periphery	Clinical benefit	Melanoma	Anti-CTLA-4 monotherapy	[28, 29]
High on-treatment CD38 + PD-1 + CD8 + T cell counts in tumor and periphery	Progressive disease	Melanoma	Anti-PD-1 monotherapy	[98]
Expansion in CD8 + T cells in the tumor	Clinical benefit	Melanoma	Anti-PD-1 monotherapy	[97]
Upregulation of genes associated with T cell activation & T cell homing in the tumor	Clinical benefit	Melanoma	Anti-PD-1 monotherapy	[24]
Increase in INF-gamma induced transcripts in the tumor	Clinical benefit	Melanoma	Anti-CTLA-4 monotherapy	[26]
Upregulation of genes involved in antigen presentation in the tumor	Clinical benefit	Melanoma	Anti-PD-1 monotherapy	[24, 99]
Proliferative response of PD-1+/CD8 + T cells in the periphery	Clinical benefit	Multiple cancer types	Anti-PD-1 monotherapy	[100,101,102]
Expansion of ICOS + CD4 + T cells with Th1 like effector phenotype in the periphery	Clinical benefit	Multiple cancer types	Anti-CTLA-4 monotherapy	[40, 41]
Expansion in Tregs in the tumor	Hyperprogressive disease	Gastric adenocarcinoma	Anti-PD-1 monotherapy	[103]
Depletion of Tregs in the tumor	Clinical benefit	Gastric adenocarcinoma	Anti-PD-1 monotherapy	[103]
Depletion of Tregs in the tumor	Clinical benefit	Melanoma	Anti-CTLA-4 monotherapy	[88, 92]
Expansion of Tregs in the periphery	Disease progression	Melanoma	Anti-CTLA-4 monotherapy	[90]
	Clinical benefit	Melanoma	Anti-CTLA-4 monotherapy	[88]
	Clinical benefit	Melanoma	Anti-PD-1 monotherapy	[104]
	None	Multiple cancer types	Anti-CTLA-4 monotherapy	[53, 57, 91]
Decline in 4PD1Hi cells in the tumor or in the periphery	Clinical benefit	Melanoma	Anti-PD-1 monotherapy	[105]
Increased richness of the TCR repertoire in the periphery	irAE	Melanoma and mCRPC	Anti-CTLA-4 monotherapy	[59, 61]
Increased clonality of the TCR repertoire in the periphery	irAE	Melanoma and mCRPC	Anti-CTLA-4 monotherapy	[62, 65]
Increased clonality of the TCR repertoire in the periphery	Clinical Benefit	Multiple tumor types	Anti-PD-1 monotherapy	[106,107,108]
Depletion in specific MDSCs subsets in the periphery	Clinical benefit	Melanoma		[88, 109]
Decline in bulk B cells coinciding with an increase in CD21^lo B cells or plasmablasts in the periphery	irAE	Melanoma	Combined anti-CTLA-4/ anti-PD-1	[110]

*Trend in association, not reaching statistical significance (P = 0.09)

Back to article page

ISSN: 1756-9966

Contact us

Submission enquiries: Access here and click Contact Us
General enquiries: info@biomedcentral.com