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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)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Tissue-resident memory (T RM ) T cells have emerged as key players in cancer immunosurveillance, and their presence has been linked to a favorable clinical outcome in solid cancer patients. Liver metastases exhibit a highly immunosuppressive tumor microenvironment, however, the role and clinical impact of T RM cell infiltration in colorectal cancer remain elusive. The expression of several tissue residency and activation biomarkers has been investigated on tumor-infiltrating lymphocytes isolated from 26 patients' colorectal cancer liver metastases (CRC liver metastases) and compared to 16 peripheral blood samples of patients with CRC liver metastases. Cytokine production was also evaluated in in vitro-activated T RM and non-T RM cells. The prognostic value of T RM cells was also assessed in a well-defined cohort of CRC liver metastases. Here we identified two subsets of T RM cells expressing CD103 and/or CD69 showing significantly higher expression of tissue residency and activation biomarkers. CD103 + CD69 + T RM cells subset showed almost exclusive expression of tumor reactivity biomarkers PD-1 and CD39. Supporting this observation, CD103 + CD69 + T RM cells showed a more oligoclonal TCR repertoire. Both T RM subsets presented higher cytotoxic and functional capacity compared to non-T RM cells. Our study shows that only the presence of CD103 + CD69 + T RM cells is associated with longer recurrence-free survival of colorectal cancer patients with liver metastases. Taken together, our work demonstrates the existence of a phenotypic heterogeneity of T RM cells in colorectal cancer liver metastases. In this study, we identified a population of CD103 + CD69 + T RM cells exhibiting the characteristics of tumor reactivity and correlated with better patients' prognosis, with potential implications in optimal therapeutic strategies determination.