Table 2. Metacore pathway analysis on differentially regulated T cell genes (p<0.05, FC±1.3).

Metacore pathway analysis was used to analyze coding genes that were differentially regulated (p<0.05, FC±1.3) between pre and post therapy T cells obtained from patients treated with either anti-PD1 alone, anti-CTLA4 alone as well as anti-CTLA4 and anti-PD1 in combination either concurrently (combination therapy) or sequentially (Sequential therapy). Table shows pathways that were differentially regulated in each group.

	Pathway	P value (FDR)
Anti PD1 therapy
1	Immune response: Role of DAP12 receptors in NK cells	2.2E-13
2	Immune response: T regulatory cell-mediated modulation of effector T cell and NK cell functions	8.5E-03
3	Immune response: IL-27 signaling pathway	1.9E-02
4	Immune response: IL-12-induced IFN-gamma production	4.2E-02
5	Immune response: Differentiation and clonal expansion of CD8+ T cells	4.2E-02
Anti CTLA4 therapy
1	Cell cycle: Transition and termination of DNA replication	5.5E-03
2	Cell cycle: Spindle assembly and chromosome separation	5.5E-03
3	Cell cycle: Nucleocytoplasmic transport of CDK/Cyclins	2.4E-02
4	Cell cycle: Chromosome condensation in prometaphase	3.0E-02
Combination Therapy (PD1+ CTLA4)
1	Cell cycle: Chromosome condensation in prometaphase	6.4E-04
2	DNA damage: ATM/ATR regulation of G1/S checkpoint	1.4E-06
3	DNA damage: ATM / ATR regulation of G2 / M checkpoint	1.4E-06
4	Cell cycle: Transition and termination of DNA replication	1.4E-06
10	Immune response: Differentiation and clonal expansion of CD8+ T cells	0.059
Sequential Therapy
1	Immune response: T regulatory cell-mediated modulation of effector T cell and NK cell functions	3.7E-02
2	Apoptosis and survival: Endoplasmic reticulum stress response pathway	4.3E-02