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Table 3. Examples of malignancies with elevated T cells associated with treatment resistance
reg
Number of
Indication Method and panel Clinical observation Ref.
patients
T cells at baseline
reg
Pan-cancer 15,512 Meta-analysis of studies Influence factors for prognosis included tumor location, Shang et al.
[91]
assessing FOXP3 in tumor tissue molecular subtype, tumor stage 2015
and OS For most solid tumors, T cells correlated with poor OS
reg
[92]
Endometrial 82 Flow cytometry using Baseline associated with treatment resistance Li et al. 2019
+
+
cancer CD4 CD25 CD127 -
Endometrial 275 IHC with FOXP3 Tumor tissue enriched for T cells at baseline and Kolben et al.
+ reg [93]
cancer Flow cytometry using CD4 associated with poor OS 2022
+ - + + -
CD25 CD127 Endometrial cancer cells expanded CD4 CD25 CD127
cells ex vivo
Breast cancer 164 Flow cytometry using CD4 + High T cells in tumor tissue and draining lymph nodes Qiu et al. 2022 [94]
reg
+
CD25 FOXP3 + associated with invasiveness
Associated with CCL5 and increased expression of
CCR5 on T cells
reg
NSCLC 64 IHC CD3 and FOXP3 High T cells in tumor tissue of patients with stage I Petersen et al.
reg
are at risk of relapse 2006 [95]
+
+
NSCLC 28 Peripheral blood and flow CD4 CD25 is higher compared to healthy subjects Karagoez et al.
+ + + - [96]
cytometry using CD4 CD25 Increased CD8 CD28 lymphocytes 2010
NSCLC 23 Peripheral blood and flow T cells elevated compared to healthy subjects Erfani et al.
reg
+ + [97]
cytometry using CD4 CD25 T cells increase depending on the stage of NSCLC 2012
+ reg
FOXP3 High intracellular CTLA-4 expression
[98]
NSCLC 36 Peripheral blood and flow T cells elevated compared to healthy subjects Hu et al. 2018
+ + reg
cytometry using CD4 CD25 T cells were negatively correlated with serum IL-17
reg
FOXP3 +
[99]
NSCLC 26 Peripheral blood and flow T cells elevated compared to healthy subjects Li et al. 2014
reg
+
cytometry using CD4 CD25 + Correlation of Th17 cells with T cells
reg
+
FOXP3 High levels of TGF-β, IL-17, IL-23
NSCLC 49 Peripheral blood and flow T cells increase depending on the stage of NSCLC Chen et al.
reg
+ + [100]
cytometry using CD4 CD25 T cells decreased after surgery 2014
+ reg
FOXP3
NSCLC 156 Peripheral blood and flow T cells produce TGF-β and IL-10 Kotsakis et al.
+ + reg [101]
cytometry using CD4 CD25 Naïve T cells elevated and correlated with poor 2016
reg
FOXP3 + outcome
High frequency of terminal T cells correlated with
reg
improved outcome
[102]
NSCLC 323 (164 with IHC for FOXP3 (clone 236A/E7) Significant High FOXP3 expression in EGFR mutation- Luo et al. 2021
(EGFR EGFR mutation) positive NSCLC
mutation) Association with poor survival
- +
NSCLC 19 (6 EGFR- Flow cytometry with CD45RA EGFR mutation is non-inflamed (no presence of CD8 T Sugiyama et al.
+ + [103]
(EGFR mutated and 13 FOXP3 CD4 (=Fraction 2) cells) 2020
mutation) EGFR-wildtype) High presence of T cells
reg
EGFR mutation induces CCL22, which induces T cells
reg
T cells response during treatment (possible predictive value)
reg
Cutaneous 40 Flow cytometry using CD4 + High baseline levels Bjoern et al.
-
+
melanoma CD25 high CD127 Foxp3 Reduction after 3 consecutive doses of ipilimumab 2016 [104]
+
+
Enrichment of CD39 HELIOS T cells
reg
Cutaneous 32 Flow cytometry using Reduction after nivolumab or pembrolizumab treatment Gambichler et
+
-
+
melanoma CD4 CD25 CD127 PD-1 + observed in patients responding to PD-1 inhibitors al. 2020 [105]
No reduction observed in patients with no response
NSCLC 31 IHC using FOXP3 for tumor Neo-adjuvant treatment with Pircher et al. [106]
tissue and flow cytometry using cetuximab/docetaxel/cisplatin showed a correlation of
+
+
+
CD4 CD25 FOXP3 for blood reduction in T cells and response
reg
T cells at diagnosis did not predict clinical response
reg
with therapy
+ [107]
NSCLC 132 Flow cytometry using CD4 High T cells and TGF-β1 levels after 1 week of Koh et al. 2020
+ - + reg
CD25 CD45RA FOXP3 treatment with PD-1 inhibitors are associated with
increased OS
High T cells at baseline associated with longer OS and
reg
PFS
+ + +
NSCLC 27 IHC and mass cytometry T cell Ratio of PD1 on CD8 /PD1 on T cells was predictive Kumagai et al.
reg
subsets of outcomes 2022 [108]