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Differential Infiltration of Key Immune T-Cell Populations Across Malignancies Varying by Immunogenic Potential and the Likelihood of Response to Immunotherapy.

Publication ,  Journal Article
Eljilany, I; Coleman, S; Tan, AC; McCarter, MD; Carpten, J; Colman, H; Naqash, AR; Puzanov, I; Arnold, SM; Churchman, ML; Spakowicz, D; Hwu, P ...
Published in: Cells
December 3, 2024

Background: Solid tumors vary by the immunogenic potential of the tumor microenvironment (TME) and the likelihood of response to immunotherapy. The emerging literature has identified key immune cell populations that significantly impact immune activation or suppression within the TME. This study investigated candidate T-cell populations and their differential infiltration within different tumor types as estimated from mRNA co-expression levels of the corresponding cellular markers. Methods: We analyzed the mRNA co-expression levels of cellular biomarkers that define stem-like tumor-infiltrating lymphocytes (TILs), tissue-resident memory T-cells (TRM), early dysfunctional T-cells, late dysfunctional T-cells, activated-potentially anti-tumor (APA) T-cells and Butyrophilin 3A (BTN3A) isoforms, utilizing clinical and transcriptomic data from 1892 patients diagnosed with melanoma, bladder, ovarian, or pancreatic carcinomas. Real-world data were collected under the Total Cancer Care Protocol and the Avatar® project (NCT03977402) across 18 cancer centers. Furthermore, we compared the survival outcomes following immune checkpoint inhibitors (ICIs) based on immune cell gene expression. Results: In melanoma and bladder cancer, the estimated infiltration of APA T-cells differed significantly (p = 4.67 × 10-12 and p = 5.80 × 10-12, respectively) compared to ovarian and pancreatic cancers. Ovarian cancer had lower TRM T-cell infiltration than melanoma, bladder, and pancreatic (p = 2.23 × 10-8, 3.86 × 10-28, and 7.85 × 10-9, respectively). Similar trends were noted with stem-like, early, and late dysfunctional T-cells. Melanoma and ovarian expressed BTN3A isoforms more than other malignancies. Higher densities of stem-like TILs; TRM, early and late dysfunctional T-cells; APA T-cells; and BTN3A isoforms were associated with increased survival in melanoma (p = 0.0075, 0.00059, 0.013, 0.005, 0.0016, and 0.041, respectively). The TRM gene signature was a moderate predictor of survival in the melanoma cohort (AUROC = 0.65), with similar findings in testing independent public datasets of ICI-treated patients with melanoma (AUROC 0.61-0.64). Conclusions: Key cellular elements related to immune activation are more heavily infiltrated within ICI-responsive versus non-responsive malignancies, supporting a central role in anti-tumor immunity. In melanoma patients treated with ICIs, higher densities of stem-like TILs, TRM T-cells, early dysfunctional T-cells, late dysfunctional T-cells, APA T-cells, and BTN3A isoforms were associated with improved survival.

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Published In

Cells

DOI

EISSN

2073-4409

Publication Date

December 3, 2024

Volume

13

Issue

23

Location

Switzerland

Related Subject Headings

  • Tumor Microenvironment
  • T-Lymphocytes
  • Neoplasms
  • Middle Aged
  • Male
  • Lymphocytes, Tumor-Infiltrating
  • Immunotherapy
  • Humans
  • Female
  • 32 Biomedical and clinical sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Eljilany, I., Coleman, S., Tan, A. C., McCarter, M. D., Carpten, J., Colman, H., … Tarhini, A. A. (2024). Differential Infiltration of Key Immune T-Cell Populations Across Malignancies Varying by Immunogenic Potential and the Likelihood of Response to Immunotherapy. Cells, 13(23). https://doi.org/10.3390/cells13231993
Eljilany, Islam, Sam Coleman, Aik Choon Tan, Martin D. McCarter, John Carpten, Howard Colman, Abdul Rafeh Naqash, et al. “Differential Infiltration of Key Immune T-Cell Populations Across Malignancies Varying by Immunogenic Potential and the Likelihood of Response to Immunotherapy.Cells 13, no. 23 (December 3, 2024). https://doi.org/10.3390/cells13231993.
Eljilany I, Coleman S, Tan AC, McCarter MD, Carpten J, Colman H, Naqash AR, Puzanov I, Arnold SM, Churchman ML, Spakowicz D, Salhia B, Marin J, Ganesan S, Ratan A, Shriver C, Hwu P, Dalton WS, Weiner GJ, Conejo-Garcia JR, Rodriguez P, Tarhini AA. Differential Infiltration of Key Immune T-Cell Populations Across Malignancies Varying by Immunogenic Potential and the Likelihood of Response to Immunotherapy. Cells. 2024 Dec 3;13(23).

Published In

Cells

DOI

EISSN

2073-4409

Publication Date

December 3, 2024

Volume

13

Issue

23

Location

Switzerland

Related Subject Headings

  • Tumor Microenvironment
  • T-Lymphocytes
  • Neoplasms
  • Middle Aged
  • Male
  • Lymphocytes, Tumor-Infiltrating
  • Immunotherapy
  • Humans
  • Female
  • 32 Biomedical and clinical sciences