Abstract: Methods of targeting CD58 signaling to enhance antitumor immunity and overcome resistance to checkpoint blockade therapy. Gene signatures associated with immune fitness were identified. Markers and therapeutic targets for such immunotherapy resistance.

Abstract: The method of enhancing anti-tumor immunity in a patient by targeting the CD58:CD2 axis uses an administered treatment to target and disrupt CMTM6 regulation of PD-L1 protein, thus enhancing the immune response and cancer immunotherapy in the patient. Targeting and disruption of CMTM6 regulation of the PD-L1 protein may be combined with additional prompting of a PD-1 blockage or adoptive cell transfer (ACT) in the patient. Targeting and disrupting CMTM6 regulation of PD-L1 protein may be initiated by administering an effective amount of antibodies to the patient, which are specific to disrupting CMTM6/PD-L1 protein interaction. Alternatively, to enhance the anti-tumor immunity in the patient, CD2 mediated signaling may be increased in order to stimulate an immune response. As another alternative to using antibodies or a CD58 mimetic, a pharmacological target to boost CD2/CD58 signaling in the patient may be identified and administered to enhance anti-tumor immunity.

Abstract: Methods of targeting CD58 signaling to enhance antitumor immunity and overcome resistance to checkpoint blockade therapy. Gene signatures associated with immune fitness were identified. Markers and therapeutic targets for such immunotherapy resistance.