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Antigen presentation by tumor infiltrating B cells influences CD4 T cell phenotype and function in primary lung cancer patient tumors
  1. Tullia Bruno1,
  2. Peggy Ebner2,
  3. Brandon Moore2,
  4. Daniel Munson2,
  5. John Mitchell2,
  6. Jeffrey Kern3,
  7. Dario AA Vignali4 and
  8. Jill Slansky2
  1. Aff1 grid.21925.3d0000000419369000University of Pittsburgh Denver CO USA
  2. Aff2 grid.241116.10000000107903411University of Colorado School of Medicine Denver CO USA
  3. Aff3 grid.240341.00000000403960728National Jewish Health Denver CO USA
  4. Aff4 grid.21925.3d0000000419369000University of Pittsburgh Pittsburgh PA USA

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Meeting abstracts

Despite improvements in surgical techniques and combined chemotherapies, the 5-year survival rate for all stages of non-small cell lung cancer (NSCLC) is only 18%. Understanding the function of tumor infiltrating lymphocytes (TILs) in NSCLC patient tumors will contribute to the development of rationally designed treatments and improved statistics. B cells in tumors (TIL-Bs) are detected in non-small cell lung cancer (NSCLC) and their frequency correlates with improved survival, however, the functional mechanism of TIL-Bs in solid tumors is not well understood. We hypothesize that TIL-Bs help generate potent, long-term immune responses against cancer by presenting tumor antigens to CD4 tumor infiltrating lymphocytes (TILs) in primary human lung tumors.

Using un-manipulated, primary human B cells from fresh tumor, tumor-adjacent, and normal (cancer-free) lung tissue per the protocol described in Figure 1, we observed that the total number of B cells at the site of the tumor versus the tumor-adjacent tissue was increased compared to other immune subsets (Figure 2). Further, in analyzing B cell markers of activation and exhaustion, we observed a spectrum of activation of TIL-Bs (Figure 2). Finally, we demonstrated that TIL-Bs present autologous tumor antigens (particularly the cancer-testis antigen XAGE-1b) to CD4 TILs in a subset of NSCLC patients; if the TIL-Bs were activated (CD69+CD27+CD21+) they polarized the CD4 TILs to T helper (anti-tumor) CD4 T cells and if the TIL-Bs were exhausted (CD69-CD27-CD21-CD95+) they polarized the CD4 TILs to T regulatory cells (pro-tumor) (Figure 3 and Figure 4). These data suggest that TIL-Bs polarize the phenotype and function of CD4 TILs in NSCLC patient tumors.


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Figure 4

In conclusion, TIL-Bs can have dual function in NSCLC patient tumors, and determining if the TIL-Bs are activated or exhausted will allow appropriate stimulation of the anti-tumor function of TIL-Bs in NSCLC patients. Ultimately, results from this study will help predict how to target TIL-B functions in future TIL-B-specific immunotherapies or in combination with current immunotherapies for NSCLC patients like blockade of the inhibitory receptor, PD-1.