The identification of surfaceome proteins is a main goal in cancer research to design
antibody-based therapeutic strategies. T cell engagers based on KLK2, a kallikrein
specifically expressed in prostate cancer (PRAD), are currently in early clinical
development. Using genomic information from different sources, we evaluated the immune
microenvironment and genomic profile of prostate tumors with high expression of KLK2.
KLK2 was specifically expressed in PRAD but it was not significant associated with
Gleason score. Additionally, KLK2 expression did not associate with the presence of
any immune cell population and T cell activating markers. A mild correlation between
the high expression of KLK2 and the deletion of TMPRSS2 was identified. KLK2 expression
associated with high levels of surface proteins linked with a detrimental response
to immune checkpoint inhibitors (ICIs) including CHRNA2, FAM174B, OR51E2, TSPAN1,
PTPRN2, and the non-surface protein TRPM4. However, no association of these genes
with an outcome in PRAD was observed. Finally, the expression of these genes in PRAD
did not associate with an outcome in PRAD and any immune populations. We describe
the immunologic microenvironment on PRAD tumors with a high expression of KLK2, including
a gene signature linked with an inert immune microenvironment, that predicts the response
to ICIs in other tumor types. Strategies targeting KLK2 with T cell engagers or antibody-drug
conjugates will define whether T cell mobilization or antigen release and stimulation
of immune cell death are sufficient effects to induce clinical activity.