The immunological synapse (IS) is a dynamic structure formed between lymphocytes and antigen presenting cells. Previous work has shown that enhancing PI3K signaling by depletion of the lipid phosphatase PTEN increases the size of the IS. In addition, cytotoxic T lymphocytes (CTLs) lacking PTEN exhibit increased killing capacity in vitro. We discovered that CTL force exertion across the IS is coordinated with the release of the toxic proteins perforin and granzyme and is correlated with specific lysis of target cells. We connected these two observations and proposed a model in which T cells use mechanical force at the IS to alter the tension of the target cell plasma membrane, increasing target cell susceptibility to perforin. Adoptive T cell therapies have shown the potential to transform the treatment of some forms of cancer and are of great interest to clinicians. We hypothesized that increasing the killing efficacy of the transferred T cells would increase the effectiveness of these treatments. Accordingly, we assessed the potential of PTEN deficiency to boost anti-cancer responses in a subcutaneous transplantable tumor model. We found that depletion of PTEN in CTLs resulted in reduced tumor rejection relative to wild type control CTLs. Our work indicated that this decrease in tumor rejection stemmed from reduced persistence of PTEN deficient CTLs in vivo. We examined the contributions to persistence from migration, survival, and homeostatic proliferation. We found that PTEN deficient CTLs have reduced migration and homeostatic proliferation, which results in diminished persistence in vivo. Our work highlights the importance of migration and homeostatic proliferation in developing an anti-tumor response.