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Healthy donor-derived T cells usually proliferate better than patients-derived T cells and are precious resources to generate off-the-shelf CAR-T cells. However, relatively little is known about the determinants that affect the efficient generation of CAR-T cells from healthy donor-derived peripheral blood mononuclear cells (PBMCs) compared with those from the patients\u2019 own PBMCs. We here examined the efficiency of CAR-T cell generation from multiple healthy donor samples and analyzed its association with the phenotypic features of the starting peripheral blood T cells. We found that CD62L expression levels within CD8+ T cells were significantly correlated with CAR-T cell expansion. Moreover, high CD62L expression within na\u00efve T cells was associated with the efficient expansion of T cells with a stem cell-like memory phenotype, an indicator of high-quality infusion products. Intriguingly, genetic disruption of CD62L significantly impaired CAR-T cell proliferation and cytokine production upon antigen stimulation. Conversely, ectopic expression of a shedding-resistant CD62L mutant augmented CAR-T cell effector functions compared to unmodified CAR-T cells, resulting in improved antitumor activity in vivo. Collectively, we identified the surface expression of CD62L as a concise indicator of potent T-cell proliferation. CD62L expression is also associated with the functional properties of CAR-T cells. These findings are potentially applicable to selecting optimal donors to massively generate CAR-T cell products.<\/jats:p>","DOI":"10.1093\/intimm\/dxae015","type":"journal-article","created":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T11:49:37Z","timestamp":1711108177000},"page":"353-364","source":"Crossref","is-referenced-by-count":10,"title":["High CD62L expression predicts the generation of chimeric antigen receptor T cells with potent effector functions"],"prefix":"10.1093","volume":"36","author":[{"given":"Hitomi","family":"Kasuya","sequence":"first","affiliation":[{"name":"Division of Immune Response, Aichi Cancer Center Research Institute , Nagoya , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haosong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Immune Response, Aichi Cancer Center Research Institute , Nagoya , Japan"},{"name":"Department of Cancer Diagnostics and Therapeutics, Nagoya University Graduate School of Medicine , Nagoya , Japan"},{"name":"Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine , Tokyo , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Ito","sequence":"additional","affiliation":[{"name":"Division of Immune Response, Aichi Cancer Center Research Institute , Nagoya , Japan"},{"name":"Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine , Tokyo , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Yoshikawa","sequence":"additional","affiliation":[{"name":"Division of Immune Response, Aichi Cancer Center Research Institute , Nagoya , Japan"},{"name":"Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine , Tokyo , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Division of Immune Response, Aichi Cancer Center Research Institute , Nagoya , Japan"},{"name":"Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine , Tokyo , Japan"},{"name":"Department of Hematology and Oncology, Nagoya City University Institute of Medical and Pharmaceutical Sciences , Nagoya , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0584-0327","authenticated-orcid":false,"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Immune Response, Aichi Cancer Center Research Institute , Nagoya , Japan"},{"name":"Department of Cancer Diagnostics and Therapeutics, Nagoya University Graduate School of Medicine , Nagoya , Japan"},{"name":"Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine , Tokyo , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Matsukawa","sequence":"additional","affiliation":[{"name":"Division of Immune Response, Aichi Cancer Center Research Institute , Nagoya , Japan"},{"name":"Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine , Tokyo , Japan"},{"name":"Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine , Nagoya , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Inoue","sequence":"additional","affiliation":[{"name":"Division of Immune Response, Aichi Cancer Center Research Institute , Nagoya , Japan"},{"name":"Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine , Tokyo , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6216-6730","authenticated-orcid":false,"given":"Yuki","family":"Kagoya","sequence":"additional","affiliation":[{"name":"Division of Immune Response, Aichi Cancer Center Research Institute , Nagoya , Japan"},{"name":"Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine , Tokyo , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,3,22]]},"reference":[{"key":"2024060804402086600_CIT0001","first-page":"945","article-title":"Disease burden affects outcomes in pediatric and young adult B-cell lymphoblastic leukemia after commercial tisagenlecleucel: a pediatric real-world chimeric antigen receptor consortium report","volume-title":"J Clin Oncol","author":"Schultz","year":"2022"},{"key":"2024060804402086600_CIT0002","first-page":"2145","article-title":"A real-world comparison of tisagenlecleucel and axicabtagene ciloleucel CAR T cells in relapsed or refractory diffuse large B cell lymphoma","volume-title":"Nat Med","author":"Bachy","year":"2022"},{"key":"2024060804402086600_CIT0003","first-page":"116","article-title":"KarMMa-RW: comparison of idecabtagene vicleucel with real-world outcomes in relapsed and refractory multiple myeloma","volume-title":"Blood Cancer J","author":"Jagannath","year":"2021"},{"key":"2024060804402086600_CIT0004","first-page":"756","article-title":"Interventions and outcomes of patients with multiple myeloma receiving salvage therapy after BCMA-directed CAR T therapy","volume-title":"Blood","author":"Van Oekelen","year":"2023"},{"key":"2024060804402086600_CIT0005","first-page":"629","article-title":"Second-line tisagenlecleucel or standard care in aggressive B-cell lymphoma","volume-title":"N Engl J Med","author":"Bishop","year":"2022"},{"key":"2024060804402086600_CIT0006","first-page":"449","article-title":"Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia","volume-title":"N Engl J Med","author":"Park","year":"2018"},{"key":"2024060804402086600_CIT0007","first-page":"597","article-title":"Integrated drug profiling and CRISPR screening identify essential pathways for CAR T-cell cytotoxicity","volume-title":"Blood","author":"Dufva","year":"2020"},{"key":"2024060804402086600_CIT0008","first-page":"563","article-title":"Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia","volume-title":"Nat Med","author":"Fraietta","year":"2018"},{"key":"2024060804402086600_CIT0009","first-page":"eabj2820","article-title":"Single-cell antigen-specific landscape of CAR T infusion product identifies determinants of CD19-positive relapse in patients with ALL","volume-title":"Sci Adv","author":"Bai","year":"2022"},{"key":"2024060804402086600_CIT0010","first-page":"492","article-title":"Na\u00efve T-cell deficits at diagnosis and after chemotherapy impair cell therapy potential in pediatric cancers","volume-title":"Cancer Discov","author":"Das","year":"2019"},{"key":"2024060804402086600_CIT0011","first-page":"1878","article-title":"Characteristics of anti-CD19 CAR T cell infusion products associated with efficacy and toxicity in patients with large B cell lymphomas","volume-title":"Nat Med","author":"Deng","year":"2020"},{"key":"2024060804402086600_CIT0012","first-page":"492","article-title":"Chimeric antigen receptor-modified T cells derived from defined CD8+ and CD4+ subsets confer superior antitumor reactivity in vivo","volume-title":"Leukemia","author":"Sommermeyer","year":"2016"},{"key":"2024060804402086600_CIT0013","first-page":"294","article-title":"Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates","volume-title":"J Clin 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Simone","year":"2019"},{"key":"2024060804402086600_CIT0039","first-page":"247","article-title":"Lymphocyte homing and leukocyte rolling and migration are impaired in","volume-title":"Immunity","author":"Arbon\u00e9s","year":"1994"},{"key":"2024060804402086600_CIT0040","first-page":"5113","article-title":"Intrinsic differences in","volume-title":"J Immunol","author":"Tang","year":"1998"},{"key":"2024060804402086600_CIT0041","first-page":"1616","article-title":"Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8+ T cells","volume-title":"J Clin Invest","author":"Gattinoni","year":"2005"},{"key":"2024060804402086600_CIT0042","first-page":"1321","article-title":"l-selectin enhanced t cells improve the efficacy of cancer immunotherapy","volume-title":"Front Immunol","author":"Watson","year":"2019"},{"key":"2024060804402086600_CIT0043","first-page":"e22560","article-title":"The shedding of CD62L (l-selectin) regulates the acquisition of lytic activity in human tumor reactive T lymphocytes","volume-title":"PLoS One","author":"Yang","year":"2011"},{"key":"2024060804402086600_CIT0044","first-page":"1190","article-title":"PSGL-1 Is an immune checkpoint regulator that promotes T cell exhaustion","volume-title":"Immunity","author":"Tinoco","year":"2016"},{"key":"2024060804402086600_CIT0045","first-page":"112436","article-title":"PSGL-1 attenuates early TCR signaling to suppress CD8(+) T cell progenitor differentiation and elicit terminal CD8(+) T cell exhaustion","volume-title":"Cell Rep","author":"Hope","year":"2023"},{"key":"2024060804402086600_CIT0046","first-page":"1068","article-title":"l-selectin: a major regulator of leukocyte adhesion, migration and signaling","volume-title":"Front Immunol","author":"Ivetic","year":"2019"}],"container-title":["International 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