Systemic T-cell and humoral responses against cancer testis antigens in hepatocellular carcinoma patients

Systemic T-cell and humoral responses against cancer testis antigens in hepatocellular carcinoma patients

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Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide due to high recurrence rates after curative treatment and being frequently diagnosed at an advanced stage.Immune-checkpoint inhibition (ICPI) has yielded impressive clinical successes in a variety of solid cancers, however results in treatment of HCC have been modest.Vaccination could be a promising treatment to synergize with ICPI and enhance response rates.Cancer testis antigens (CTAs) were recently discovered to be widely expressed in HCC and expression in macroscopically tumor-free tissues correlated with recurrence, implying the presence of micro-satellites.

To determine whether CTAs are immunogenic in HCC patients, we analyzed systemic T-cell and humoral responses against navy drapery fabric seven CTAs in 38 HCC patients using a multitude of techniques; flowcytometry, ELISA and whole antigen and peptide stimulation assays.CTA-specific T-cells were detected in all (25/25) analyzed patients, of which most had a memory phenotype but did not exhibit unequivocal signs of chronic stimulation or recent antigen encounter.Proliferative CD4+ and CD8+ T-cell responses against these CTAs were kali ws 6.2 found in 14/16 analyzed HCC patients.CTA-peptide stimulation-induced granzyme B, IL2, and TNFa in 8/8 analyzed patients, including two MAGEA1 peptides included based on in silico prediction.

Finally, IgG responses were observed in 13/32 patients, albeit with low titers.The presence of CD4+ and CD8+ T-cells and IgG responses shows the immunogenicity of these CTAs in HCC-patients.We hypothesize that vaccines based on these tumor-specific antigens may boost preexisting CTA-specific immunity and could enhance therapeutic efficacy of ICPI in advanced HCC.