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Objective Vaccinated patients with cancer in follow-up studies showed a high seropositivity rate but impaired antibody titres and T cell responses following mRNA vaccine against COVID-19. Besides clinical characteristics and the type of anticancer treatment before vaccination, the identification of patients susceptible to non-response following vaccination using immunological markers is worth to be investigated.Methods and analysis All patients (n=138, solid cancers) were included in the CACOV-VAC Study comprising three cohorts ((neo)-adjuvant, metastatic and surveillance). Immune responses were assessed using, respectively, anti-receptor-binding domain (RBD) SARS-CoV-S-IgG assay and interferon-γ ELISpot assay 3 months following the prime vaccination dose. Immunophenotyping of T cells and immunosuppressive cells from peripheral blood was performed before the prime dose. The serological threshold 3563 AU/mL was used to discriminate non-responders or suboptimal responders versus responders.Results Most patients achieved seroconversion after receiving the two doses of vaccine (97.6%). The median serological level of anti-RBD SARS-CoV-S-IgG was equal to 3029 for patients at the metastatic stage. The patient’s age was the main demographic characteristic that influenced vaccine efficacy. Among the immunological parameters measured at baseline, lower TIGIT (T cell immunoreceptor with Ig and ITIM domains) expression on CD8 T cells was associated with a better vaccine immunogenicity both in terms of humoral and cellular immune responses.Conclusion Despite a high seroconversion rate, median serological levels of patients with cancer, particularly elderly patients, were below the threshold equal to 3563 AU/mL considered as a humoral correlate of protection against SARS-CoV-2. Our findings suggest that the inhibitory receptor TIGIT might be an interesting predictive biomarker of COVID-19 vaccine immunogenicity and beyond in an anticancer vaccine context.Trial registration number ClinicalTrials.gov Registry (NCT04836793).

Background The positive role of CD8+ tumor-infiltrating lymphocytes (TIL) in patients with colorectal cancer (CRC) has been well described but the prognostic value of CD4 T cell subsets remained to be investigated. In this study, we expanded TIL from surgically resected liver metastases of patients with CRC and characterized the phenotype and the prognostic value of expanded-CD4 T cells.Methods Liver metastases were surgically resected from 23 patients with CRC. Tumors were enzymatically digested and cultured in high dose of interleukin-2 for up to 5 weeks. T cell phenotype and reactivity of cultured-T cells were measured by flow cytometry and correlated with patients’ clinical outcomes.Results We successfully expanded 21 over 23 TIL from liver metastases of patients with CRC. Interestingly, we distinguished two subsets of expanded T cells based on T cell immunoglobulin mucin domain-containing protein 3 (TIM-3) expression. Medians fold expansion of expanded T cells after rapid expansion protocol was higher in CD3+TIM-3low cultures. In an attempt to investigate the correlation between the phenotype of expanded CD4 T cells and clinical outcomes, we observed on one hand that the level of Tregs in culture as well as the expression of both PD1 and TIM-3 by expanded T cells was not correlated to the clinical outcomes. Interestingly, on the other hand, cultures containing high levels of Th17 cells were associated with a poor prognosis (p=0.0007).Conclusions Our data confirmed the presence of Th17 cells in expanded T cells from liver metastases. Among CD4 T cell characteristics investigated, TIM-3 but not programmed cell death protein 1 predicted the expansion capacity of TIL while only the Th17 phenotype showed correlation with patients’ survival, suggesting a particular role of this T cell subset in CRC immune contexture.Trial registration number NCT02817178.