Greater upregulation of Ki67 in CD4<sup>+</sup> central memory cells significantly differentiated responders and non-responders after one cycle of treatment (p=0.0086, area under the curve (AUC)=0.74, 95% CI 0.59 to 0.88), while higher on-treatment TIM-3 frequency within CD8<sup>+</sup> T cells differentiated patients who experienced severe toxicity (p=0.0086, AUC=0.74, 95% CI 0.59 to 0.88).<h4>Conclusions</h4>We here show that response and toxicity to cICB in advanced melanoma are driven by distinct immune features evident after only one cycle of treatment. This evidence concerns the gene HAVCR2 and melanoma.