Method and treatment

A method of treating cancer in a subject that has been identified as being non-responsive to treatment with an immune checkpoint inhibitor, comprising:

• (a) administering an effective amount of an agent which inhibits arginase 1 activity and/or targets cells expressing arginase 1, for sufficient time to render the subject responsive to the immune checkpoint inhibitor;
• and
• (b) administering an effective amount of the immune checkpoint inhibitor, optionally in combination with further administration of the agent which inhibits arginase 1 activity and/or targets cells expressing arginase 1 wherein the subject has been identified as non-responsive to the immune checkpoint inhibitor by
• (i) providing a positive response control from one or more positive responders who have formed a clinical response to the treatment, and a negative response control from one or more non-responders who have not formed a clinical response to the treatment, each response control representing a distribution of cells of a blood sample from the positive responder(s) and the non-responder(s) within a series of classes, wherein the distribution of cells is according to the expression by cells of the sample of a group of biomarkers so that cells having the same expression of biomarkers from the group of biomarkers are classified in the same class, wherein the group of biomarkers comprises at least 5 markers selected from CD45, CD45RA, CD45RO, CD3, CD4, CD8, CD19, CD20, CD14, CD15, CD16, CD11b, CD11c, CD66b, CD304, FoxP3, CD123, CD127, CD25, CD33, CD56, HLA-DR, IgD, CD27, CD86, FCRL3, CD274 (PD-1), CD279 (PD-L1), TIGIT, CD38, Ki67, Granzyme B, CD134 (OX40), CD192 (CCR2), CD194 (CCR4), CD195 (CCR5), CD196 (CCR6), CD197 (CCR7), Integrin beta7, CLA, CD183 (CXCR3), CD185, (CXCR5), CCR10, GM-CSFR alpha chain, and intracellular arginase 1;
• (ii) determining the distribution of cells in a blood sample from the subject within the series of classes of the positive response control and the negative response control;
• (iii) comparing the distribution of the cells of the sample from the subject within the series of classes with the negative response control and/or the positive response control, wherein the subject is determined to be non-responsive to the treatment if the distribution of cells of the sample from the subject within the series of classes is substantially the same as the distribution of cells within the series of classes represented by the negative response control and/or is not the same as the distribution of cells within the series of classes represented by the positive response control.

A method of determining whether a subject suffering from cancer will be non-responsive to treatment with an immune checkpoint inhibitor, the method comprising:

• (i) providing a positive response control from one or more positive responders who have formed a clinical response to the treatment, and a negative response control from one or more non-responders who have not formed a clinical response to the treatment, each response control representing a distribution of cells of a blood sample from the positive responder(s) and the non-responder(s) within a series of classes, wherein the distribution of cells is according to the expression by cells of the sample of a group of biomarkers so that cells having the same expression of biomarkers from the group of biomarkers are classified in the same class, wherein the group of biomarkers comprises intracellular arginase 1 and at least 4 markers selected from CD45, CD45RA, CD45RO, CD3, CD4, CD8, CD19, CD20, CD14, CD15, CD16, CD11b, CD11c, CD66b, CD304, FoxP3, CD123, CD127, CD25, CD33, CD56, HLA-DR, IgD, CD27, CD86, FCRL3, CD274 (PD-1), CD279 (PD-L1), TIGIT, CD38, Ki67, Granzyme B, CD134 (OX40), CD192 (CCR2), CD194 (CCR4), CD195 (CCR5), CD196 (CCR6), CD197 (CCR7), Integrin beta7, CLA, CD183 (CXCR3), CD185, (CXCR5), CCR10, and GM-CSFR alpha chain;
• (ii) determining the distribution of cells in a blood sample from the subject within the series of classes of the positive response control and the negative response control;
• (iii) comparing the distribution of the cells of the sample from the subject within the series of classes with the negative response control and/or the positive response control, wherein the subject is determined to be non-responsive to the treatment if the distribution of cells of the sample from the subject within the series of classes is substantially the same as the distribution of cells within the series of classes represented by the negative response control and/or is not the same as the distribution of cells within the series of classes represented by the positive response control.