Polyfunctional pathogen-specific CD4+ T cells reside in the lungs and tumors of NSCLC patients

Oja, A. E.; Morgana, F.; Hagen, R.; Ghandour, C. A.; Nolte, M. A.; Rooijakkers, S.; van Lier, R. A. W.; Bardoel, B. W.; Hombrink, P.

doi:10.1101/2022.02.16.479923

bioRxiv · 10.1101/2022.02.16.479923

Polyfunctional pathogen-specific CD4+ T cells reside in the lungs and tumors of NSCLC patients

Oja, A. E.·Morgana, F.·Hagen, R.·Ghandour, C. A.·Nolte, M. A.·Rooijakkers, S.·van Lier, R. A. W.·Bardoel, B. W.·Hombrink, P.

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Abstract

Local T cell responses are required for optimal protection of the lungs against airborne pathogens. This localized protection is mediated by various immune cells, including resident memory T cells (TRM). While human lung CD8+ TRM line the epithelium and are enriched for recognition of respiratory viruses, we found CD4+ TRM to exhibit more heterogeneous localization patterns, surrounding airways, forming clusters in the lung parenchyma, and lining the epithelium. This heterogeneity was also reflected functionally, as lung CD4+ TRM were enriched for recognition of diverse classes of respiratory pathogens. Upon stimulation, lung CD4+ TRM expressed different polyfunctional cytokine profiles depending on the pathogen recognized. CD4+ TRM responding to respiratory viruses and bacteria were biased for production of IFN-{gamma} and IL-17, respectively. Strikingly, pathogen-specific CD4+ TRM also represent a significant fraction in NSCLC tumors that remained polyfunctional despite high PD-1 expression. These findings are not only important for vaccine design, but also provide a rationale for reinvigorating anti-tumor immunity through triggering of polyfunctional pathogen-specific CD4+ tumor infiltrating lymphocytes.

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Oja, A. E., Morgana, F., Hagen, R., Ghandour, C. A., Nolte, M. A., Rooijakkers, S., van Lier, R. A. W., Bardoel, B. W., Hombrink, P.. 2022-02-19. Polyfunctional pathogen-specific CD4+ T cells reside in the lungs and tumors of NSCLC patients. https://doi.org/10.1101/2022.02.16.479923

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