Combinations of Brutons tyrosine kinase (Btk) inhibitors, e.g., l-((R)-3-(4-amino-3-(4- phenoxyphenyl)- 1 H-pyrazolo [3,4-d]pyrimidin- 1 -yl)piperidin- 1 -yl)prop-2-en- 1 -one, with immunotherapy are provided. Also provided are methods of treating cancers, and autoimmune disorders by administering combinations of Brutons tyrosine kinase (Btk) inhibitors, e.g., 1- ((R)-3-(4-amino-3-(4-phenoxyphenyl)-lH-pyrazolo[3,4-d]pyrimidin-l-yl)piperidin-l-yl)prop-2- en-l-one, and an immune checkpoint inhibitor.