A recent research letter in Nature Medicine by Alena Gros et al has opened a novel window for treatment of cancer tumors using personalized neoantigen-specific lymphocytes. In their study they have successfully identified patient-specific repertoire of tumor reactive CD8+ lymphocytes from peripheral blood.
They have reported that intratumoral expression of the programmed cell death 1 (PD-1) receptor can guide the identification of the patient-specific repertoire of tumor-reactive CD8+ lymphocytes that reside in the tumor. Also they say that they have investigated whether PD-1 expression on peripheral blood lymphocytes could be used as a biomarker to detect T cells that target neoantigens.
By using a high-throughput personalized screening approach, they identified neoantigenspecific lymphocytes in the peripheral blood of three of four melanoma patients which is interesting result.
Furthermore they showed that neoantigen-specific T cells and gene-engineered lymphocytes expressing neoantigenspecific T cell receptors (TCRs) isolated from peripheral blood recognized autologous tumors. Notably, the tumor-antigen specificities and TCR repertoires of the circulating and tumorinfiltrating CD8+PD-1+ cells appeared similar, implying that the circulating CD8+PD-1+ lymphocytes could provide a window into the tumor-resident antitumor lymphocytes. Thus, expression of PD-1 identifies a diverse and patient-specific antitumor T cell response in peripheral blood, providing a novel noninvasive strategy to develop personalized therapies using neoantigenreactive lymphocytes or TCRs to treat cancer.
However low frequency of such lymphocytes in the circulation is still the big challenge for this technique in order to make it applicable in the field of cancer treatment.
Gros, Alena, et al. “Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients.” Nature medicine22.4 (2016): 433-438.