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The role of CMTM8 in tumour immune microenvironment (TIME) remains unknown. The aim was to investigate the relationship between CMTM8 and antitumour immunity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Lentiviral system was established to achieve functional edition of CMTM8. CMTM8 in tumour progression and TIME was investigated by using subcutaneous xenograft mice tumour models. CMTM8 targeting was achieved using an adeno\u2010associated virus (AAV)\u2013based shRNA vector.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Clinical data showed that high expression of CMTM8 in melanoma and colorectal cancer is associated with lower patient survival rates and poorer intra\u2010tumoural immune cell infiltration. Mouse melanoma and colon cancer models, CMTM8 expression markedly accelerated tumour growth by regulating intra\u2010tumoural infiltration of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells and NK cells. RNA sequencing of CMTM8\u2010overexpressed B16 cells showed that Notch pathway is significantly up\u2010regulated, and blockade of Notch pathway\n                      <jats:italic>in vivo<\/jats:italic>\n                      resulted in lower intra\u2010tumoural infiltration of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells and NK cells, and confined tumour progression. CMTM8 could down\u2010regulate the EGFR pathway by promoting endocytosis of EGFR, possible leading to higher expression of Notch1. Similar this observed in human colon cancer in a PBMC\u2010engrafted NCG model. Besides, we developed the CMTM8\u2010targeting adeno\u2010associated virus, which effectively up\u2010regulated intra\u2010tumoural infiltration of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells and NK cells and inhibited tumour growth.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>Tumour\u2010intrinsic CMTM8 could possibly regulate TIME via EGFR\u2010Notch axis and that CMTM8 is a promising target for tumour immunotherapy, especially for treatment of colorectal cancer or melanoma patients.<\/jats:p>\n                  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