Skip to main content

Immune profiling of circulating T cells and TILs following neoadjuvant ipilimumab and chemotherapy in non-small cell lung cancer (NSCLC).

Publication ,  Conference
Yi, J; Clarke, JM; Healy, P; Wang, XF; Shoemaker, D; Onaitis, MW; Dumbauld, C; Osborne, R; Crawford, J; Harpole, D; D'Amico, TA; Dunphy, F ...
Published in: Journal of Clinical Oncology
March 1, 2017

26 Background: Ipilimumab (Ipi) is a humanized CTLA-4 antibody that blocks binding of CTLA-4 to B7, permitting T cell activation through CD28. Phased in Ipi added to chemotherapy (C) may enhance efficacy in NSCLC. Methods: Patients with stage 2 or 3A NSCLC received neoadjuvant carboplatin AUC6 plus paclitaxel 200 mg/m every 21 days for 3 cycles and Ipi (10 mg/kg) was given on day 1 for cycles 2 and 3. Blood for immune profiling of circulating T cells was collected at baseline, after chemotherapy alone, and after chemotherapy plus Ipi. Tumor infiltrating lymphocytes (TIL) were derived from 7 available tumors. Polychromatic flow cytometry (PFC) analyses were performed on peripheral blood mononuclear cells (PBMC) and TIL. Objective response rates were assessed according to RECIST 1.1 criteria. Results: Of the 24 patients enrolled on this study, objective responses after 3 cycles of neoadjuvant C plus ipi included 2 PD, 8 SD, and 14 PR. Phenotypic analyses revealed that PBMC from all 24 patients were highly activated following two cycles of Ipi (cycle 3) as evidenced by significantly increased frequencies of CD28, ICOS, HLA-DR, PD-1, and CTLA-4 expressing CD4+ cells; and ICOS, HLA-DR, and CTLA-4 expressing CD8+ cells. The frequencies of Tregs were highly variable among the 24 participants. Two of the 24 participants had levels of MDSC cells above 15%. TIL contained far greater frequencies of activated CD4+ and CD8+ cells than found in the PBMC at cycle 3. Tumor associated antigen (TAA)-specific CD4+ or CD8+ cells were detected at baseline in 4 patients (24%), but their relative frequencies remained unaltered by Ipi therapy. No patients developed detectable de novo TAA reactivities while on Ipi therapy. Conclusions: Combined neoadjuvant Ipi plus chemotherapy produced significantly increased frequencies of highly activated CD4+ and CD8+ populations in the peripheral blood and the tumor microenvironment. TAA-specific CD4+ or CD8+ cells were detected in PBMC at baseline in a subset of patients. No TAA-reactive T cells were detected among the 7 TIL samples analyzed. Analysis for predictive or pharmacodynamic biomarkers is ongoing. Clinical trial information: NCT01820754.

Duke Scholars

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

March 1, 2017

Volume

35

Issue

7_suppl

Start / End Page

26 / 26

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Yi, J., Clarke, J. M., Healy, P., Wang, X. F., Shoemaker, D., Onaitis, M. W., … Weinhold, K. (2017). Immune profiling of circulating T cells and TILs following neoadjuvant ipilimumab and chemotherapy in non-small cell lung cancer (NSCLC). In Journal of Clinical Oncology (Vol. 35, pp. 26–26). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.2017.35.7_suppl.26
Yi, John, Jeffrey Melson Clarke, Patrick Healy, Xiaofei F. Wang, Debra Shoemaker, Mark W. Onaitis, Chelsae Dumbauld, et al. “Immune profiling of circulating T cells and TILs following neoadjuvant ipilimumab and chemotherapy in non-small cell lung cancer (NSCLC).” In Journal of Clinical Oncology, 35:26–26. American Society of Clinical Oncology (ASCO), 2017. https://doi.org/10.1200/jco.2017.35.7_suppl.26.
Yi J, Clarke JM, Healy P, Wang XF, Shoemaker D, Onaitis MW, et al. Immune profiling of circulating T cells and TILs following neoadjuvant ipilimumab and chemotherapy in non-small cell lung cancer (NSCLC). In: Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2017. p. 26–26.
Yi, John, et al. “Immune profiling of circulating T cells and TILs following neoadjuvant ipilimumab and chemotherapy in non-small cell lung cancer (NSCLC).Journal of Clinical Oncology, vol. 35, no. 7_suppl, American Society of Clinical Oncology (ASCO), 2017, pp. 26–26. Crossref, doi:10.1200/jco.2017.35.7_suppl.26.
Yi J, Clarke JM, Healy P, Wang XF, Shoemaker D, Onaitis MW, Dumbauld C, Osborne R, Crawford J, Harpole D, D’Amico TA, Dunphy F, Christensen J, Ready N, Weinhold K. Immune profiling of circulating T cells and TILs following neoadjuvant ipilimumab and chemotherapy in non-small cell lung cancer (NSCLC). Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2017. p. 26–26.

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

March 1, 2017

Volume

35

Issue

7_suppl

Start / End Page

26 / 26

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences