Products and uses thereof for predicting the sensitivity of a subject to cancer immunotherapy involving an anti-pd(l)1 and an anti-angiogenic agent, and for selecting optimized therapy

An in vitro or ex vivo method of predicting, assessing or monitoring the sensitivity or resistance of a subject having a cancer to a therapy combining i) an immunotherapeutic agent, in particular an anti-PD-1, or anti-PD-L1, monoclonal antibody, and ii) an anti-angiogenic agent, after one or several treatment steps in the subject, wherein the method comprises:

• a step a) of determining in a tumor sample of the subject, the proportion of CD8+ T-cells among live CD45+CD3+ T cells, and a step b) of comparing said live CD8+CD3+CD45+ T cells proportion to a CD8+CD3+CD45+ T cells reference proportion, a proportion of live CD8+CD3+CD45+ T cells below (<) the CD8+CD3+CD45+ T cells reference proportion being indicative of resistance of the subject to the combination therapy and a proportion of live CD8+CD3+CD45+ T cells superior or equal to (≥) the CD8+CD3+CD45+ T cells reference proportion being indicative of sensitivity of the subject to the combination therapy;
• a step a) of determining in a blood sample of the subject, the expression level of effector memory (EM) CD4+ T cells expressing the alpha-4 beta-7 integrin (a4b7+ EM CD4+ T cells), cutaneous lymphocyte antigen selectin (CLA+ EM CD4+ T cells), CD49a integrin (CD49a+EM CD4+ T cells) and/or CXCR3 chemokine receptor (CXCR3+ Th1 CD4+ T cells), and a step b) of comparing said expression level(s) to a4b7+ EM CD4+ T cells, CLA+ EM CD4+ T cells, CD49a+ EM CD4+ T cells and/or CXCR3+ Th1 CD4+ T cells reference expression level(s), (an) expression level(s) superior or equal to (≥) the reference expression level(s) being indicative of sensitivity of the subject to the combination therapy, and (an) expression level(s) below (<) the reference expression level(s) being indicative of resistance of the subject to the combination therapy;
• a step a) of determining in a blood plasma sample or in a tumor supernatant sample of the subject, the concentration of VEGFA, VEGFD, CXCL8 and/or IL6 protein(s), and a step b) of comparing said concentration(s) to VEGFA, VEGFD, CXCL8 and/or IL6 protein(s) reference concentration(s), concentration(s) superior or equal to (≥) the reference concentration(s) being indicative of resistance of the subject to the combination therapy, and concentration(s) below (<) the reference concentration(s) being indicative of sensitivity of the subject to the combination therapy;
• and/or
• a step of determining in cancerous cells of a tumor sample of the subject, the number of somatic alterations, a somatic copy number alteration score or genomic instability score (“SCNA score”) above (>) a reference score being indicative of resistance of the subject to the combination therapy, and a SCNA score equal to or below (≤) the reference score being indicative of sensitivity of the subject to the combination therapy.