Journal article
Differential Infiltration of Key Immune T-Cell Populations Across Malignancies Varying by Immunogenic Potential and the Likelihood of Response to Immunotherapy
Cells (Basel, Switzerland), Vol.13(23), 1993
12/03/2024
DOI: 10.3390/cells13231993
PMCID: PMC11640164
PMID: 39682743
Abstract
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.
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.
In melanoma and bladder cancer, the estimated infiltration of APA T-cells differed significantly (
= 4.67 × 10
and
= 5.80 × 10
, respectively) compared to ovarian and pancreatic cancers. Ovarian cancer had lower TRM T-cell infiltration than melanoma, bladder, and pancreatic (
= 2.23 × 10
, 3.86 × 10
, and 7.85 × 10
, 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 (
= 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).
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.
Details
- Title: Subtitle
- Differential Infiltration of Key Immune T-Cell Populations Across Malignancies Varying by Immunogenic Potential and the Likelihood of Response to Immunotherapy
- Creators
- Islam Eljilany - Moffitt Cancer CenterSam Coleman - Huntsman Cancer InstituteAik Choon Tan - Huntsman Cancer InstituteMartin D McCarter - University of Colorado DenverJohn Carpten - University of Southern CaliforniaHoward Colman - Huntsman Cancer InstituteAbdul Rafeh Naqash - OU HealthIgor Puzanov - Roswell Park Comprehensive Cancer CenterSusanne M Arnold - University of KentuckyMichelle L ChurchmanDaniel Spakowicz - The Ohio State UniversityBodour Salhia - University of Southern CaliforniaJulian Marin - Indiana University IndianapolisShridar Ganesan - Rutgers, The State University of New JerseyAakrosh Ratan - University of VirginiaCraig Shriver - Walter Reed National Military Medical CenterPatrick Hwu - Moffitt Cancer CenterWilliam S DaltonGeorge J Weiner - University of Iowa Health CareJose R Conejo-Garcia - Moffitt Cancer CenterPaulo Rodriguez - Moffitt Cancer CenterAhmad A Tarhini - Moffitt Cancer Center
- Resource Type
- Journal article
- Publication Details
- Cells (Basel, Switzerland), Vol.13(23), 1993
- DOI
- 10.3390/cells13231993
- PMID
- 39682743
- PMCID
- PMC11640164
- NLM abbreviation
- Cells
- ISSN
- 2073-4409
- eISSN
- 2073-4409
- Publisher
- MDPI
- Grant note
- 69-21295-01-01 / ORIEN FOUNDATION NOVA and Community Foundation of Tampa Bay
- Language
- English
- Date published
- 12/03/2024
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Internal Medicine
- Record Identifier
- 9984757683202771
Metrics
9 Record Views