Immunological biomarker for predicting clinical effect of cancer immunotherapy

Abstract

The present invention relates to the prediction of responsiveness to cancer immunotherapy of a subject based on the T-cell composition of the subject, and a therapeutic method using cancer immunotherapy based on the prediction. The present invention also provides a method for improving or maintaining responsiveness to cancer immunotherapy of a subject. Responsiveness to cancer immunotherapy is predict by determining a relative value of a CD4+ T-cell subpopulation, dendritic cell subpopulation, and/or CD8+ T-cell subpopulation correlated with a dendritic cell stimulation in an anti-tumor immune response in a sample derived from a subject. A composition for treating or preventing cancer comprising cells such as CD62LlowCD4+ T-cells is also provided.

1 . A method for treating or preventing cancer, comprising administering a composition comprising CD62L low CD4 +  T-cell. 
     
     
         2 . The method of  claim 1 , the composition further comprising a Foxp3 + CD25 + CD4 +  T-cell. 
     
     
         3 . The method of  claim 1 , wherein the composition is administered concomitantly with cancer immunotherapy. 
     
     
         4 . The method of  claim 1 , characterized in that the composition is administered in combination with an immune checkpoint inhibitor. 
     
     
         5 . The method of  claim 4 , wherein the immune checkpoint inhibitor is selected from the group consisting of a PD-1 inhibitor, a PD-L1 inhibitor, and CTLA-4 inhibitor. 
     
     
         6 . The method of  claim 5 , wherein the PD-1 inhibitor is an anti-PD-1 antibody that inhibits an interaction between PD-1 and PD-L1. 
     
     
         7 . The method of  claim 5 , wherein the PD-L1 inhibitor is an anti-PD-L1 antibody that inhibits an interaction between PD-1 and PD-L1. 
     
     
         8 . The method of  claim 5 , wherein the PD-1 inhibitor or PD-L1 inhibitor comprises nivolumab, pembrolizumab, durvalumab, atezolizumab, or avelumab. 
     
     
         9 . The method of  claim 1 , the composition further comprising a CD62L low CD8 +  T-cell. 
     
     
         10 . The method of  claim 1 , wherein the composition makes cancer immunotherapy effective in a subject to whom cancer immunotherapy is predicted to be ineffective. 
     
     
         11 . The method of  claim 1  for sustaining an effect of cancer immunotherapy. 
     
     
         12 . The method of  claim 1 , wherein the CD62L low  CD4 +  T-cell is from a subject to whom the composition is administered. 
     
     
         13 . A method of manufacturing a composition for treating or preventing cancer comprising CD62L low CD4 +  T-cells, comprising purifying CD62L low CD4 +  T-cells from a T-cell population derived from a human. 
     
     
         14 . The method of  claim 13 , wherein the purifying comprises removing a CD62L high expression cell from a T-cell population. 
     
     
         15 . A kit comprising a substance, which specifically binds to CD62L, for purifying CD62L low CD4 +  T-cells.