bims-tuinly 2024-11-03 papers

bims-tuinly

Biomed News

on Tumor-infiltrating lymphocytes therapy

Issue of 2024–11–03
seven papers selected by
Pierpaolo Ginefra, Ludwig Institute for Cancer Research

Spatial context of immune checkpoints as predictors of overall survival in patients with resectable colorectal cancer independent of standard TNM stages.
WNT/β-catenin Signaling and CD8+ Tumor-infiltrating Lymphocytes in Tremelimumab Plus Durvalumab for Advanced Hepatocellular Carcinoma.
Chemokine Profile Is Different in Normal Testis Compared to Seminoma - Especially in Tumor Infiltrating Lymphocytes.
The Expression of PDL-1 and PD1 in the Microenvironment of Oral Squamous Cell Carcinoma.
Systematic analysis of human colorectal cancer scRNA-seq revealed limited pro-tumoral IL-17 production potential in gamma delta T cells.
The recent progress of γδ T cells and its targeted therapies in rheumatoid arthritis.
Comprehensive assessment of the association between tumor-infiltrating immune cells and the prognosis of renal cell carcinoma.

Cancer Res Commun. 2024 Nov 01.

Spatial context of immune checkpoints as predictors of overall survival in patients with resectable colorectal cancer independent of standard TNM stages.

Hao Kong, Qingxin Yang, Chunwei Wu, Xiangji Wu, Xinrui Yan, Li-Bin Huang, Lu Chen, Zong-Guang Zhou, Ping Wang, Hong Jiang.

While immune checkpoint blockade (ICB) therapy has shown promising results in a small subset of colorectal cancer patients with high microsatellite instability (MSI-H), the majority of patients with colorectal cancer do not respond to ICB therapy. The main obstacle to the success of immunotherapy in cancer treatment is the exhaustion of tumor-infiltrating lymphocytes (TILs). Elucidating the spatial organization of immune checkpoints within the tumor microenvironment could pave the way for the development of novel prognostic tools and therapeutic strategies to enhance antitumor immune responses. To clarify the spatial and functional diversity of tumor-infiltrating lymphocytes (TILs) in the colorectal tumor microenvironment (TME), we performed multiplexed IHC to examine the exhaustion of TILs in the TME (the expression of PD-1 and TIM-3 (T-cell immunoglobulin and mucin-domain-containing protein 3), which are major biomarkers of T-cell exhaustion) and Lasso-Cox analyses of the correlation between CRC prognosis and TME features. For proof of concept, the antitumor efficacy of TIM-3 and PD-1 dual blockade in CRC was further evaluated in a CT26 subcutaneous tumor model of human CRC. We found that the spatial context of PD-1 and TIM-3 successfully predicted the overall survival of CRC patients independent of TNM stage. Dual targeting of PD-1 and TIM-3 in mouse tumor models inhibited tumor progression and reduced T-cell exhaustion, indicating a potential strategy for improving the clinical treatment of CRC.

DOI: https://doi.org/10.1158/2767-9764.CRC-24-0270
In Vivo. 2024 Nov-Dec;38(6):38(6): 2774-2781

WNT/β-catenin Signaling and CD8+ Tumor-infiltrating Lymphocytes in Tremelimumab Plus Durvalumab for Advanced Hepatocellular Carcinoma.

Akifumi Kuwano, Kosuke Tanaka, Junro Takahira, Hideo Suzuki, Yoshihiro Ohishi, Kenta Motomura.

   BACKGROUND/AIM: Tremelimumab plus durvalumab is an approved first-line therapy for advanced hepatocellular carcinoma (HCC). Previous studies identified WNT/β-catenin mutations or CD8+ tumor-infiltrating lymphocytes (TILs) as biomarkers that can predict responsiveness to immune checkpoint inhibitor therapy in HCC. However, biomarkers for effectiveness of tremelimumab plus durvalumab in HCC have not been reported. This study investigated whether evaluation of WNT/β-catenin signaling and CD8+ TILs by immunohistochemical staining of tumor biopsy tissues can predict the response to tremelimumab plus durvalumab in patients with HCC.
PATIENTS AND METHODS: Fifteen HCC patients who underwent tumor biopsies were classified into three groups based on WNT/β-catenin signal activation and CD8+ TIL infiltration. The clinical responses to treatment in the groups were evaluated.
RESULTS: Four patients had HCC with WNT/β-catenin signal inactivation and high-level CD8+ TIL infiltration, four patients had HCC with WNT/β-catenin signal activation and low-level CD8+ TIL infiltration, and seven patients had WNT/β-catenin signal activation and high-level CD8+ TIL infiltration or WNT/β-catenin signal inactivation and low-level CD8+ TIL infiltration. A better response rate was observed in the WNT/β-catenin signal inactivation and high-level CD8+ TIL infiltration group, and a worse response rate was observed in the WNT/β-catenin signal activation and low-level CD8+ TIL infiltration group.
CONCLUSION: Although the present study involved a small number of patients, the findings suggest that the efficacy of tremelimumab plus durvalumab may be affected by WNT/β-catenin signaling and CD8+ TIL infiltration.

Keywords:  CD8+ tumor-infiltrating lymphocytes; Hepatocellular carcinoma; WNT/β-catenin signal; objective response; tremelimumab plus durvalumab

DOI:  https://doi.org/10.21873/invivo.13757
Anticancer Res. 2024 Nov;44(11): 4961-4967

Chemokine Profile Is Different in Normal Testis Compared to Seminoma - Especially in Tumor Infiltrating Lymphocytes.

Jonas M Händelin, Hanna-Riikka Teppo, Kirsi-Maria Haapasaari, Riina K Ollikainen, Janette Kemppainen, Hanne Kuitunen, Outi Kuittinen, Milla E L Kuusisto.

   BACKGROUND/AIM: Testicular cancers, particularly seminomas and non-seminomas, generally have a favorable prognosis, although a small subset of patients experience mortality. Current knowledge of clinical markers associated with relapse and poor prognosis in seminoma is limited. Chemokines, key proteins in the tumor microenvironment, are underexplored in seminoma prognosis. Additionally, tumor-infiltrating lymphocytes (TILs), which play a critical role in cancer prognosis, require further investigation in the context of seminoma.
PATIENTS AND METHODS: Samples from 25 seminoma patients and 24 control patients who underwent orchiectomy were immunohistochemically (IHC) stained for chemokines CXCR4, CXCR5, and their ligands CXCL12, CXCL13, and the proliferation marker Ki-67. The associations between IHC results and clinical presentations were examined.
RESULTS: Chemokine profiles differed between seminoma and normal testis. The expression of chemokines in TILs in seminoma samples was especially over-expressed. The cytoplasmic expression of CXCL13 in TILs multiplied by the percentage of TILs in each sample, appeared to approach statistical significance concerning the likelihood of relapse.
CONCLUSION: The involvement of TILs in seminoma biology warrants further investigation, especially their role in the tumor micro-environment and pathogenesis. Chemokine and Ki-67 expression in TILs could serve as potential markers for assessing seminoma prognosis.

Keywords:  CXCL13; Ki-67 chemokines; Seminoma; TILs; cytokines; prognosis

DOI:  https://doi.org/10.21873/anticanres.17321
Asian Pac J Cancer Prev. 2024 Oct 01. pii: 91346. [Epub ahead of print]25(10): 3471-3479

The Expression of PDL-1 and PD1 in the Microenvironment of Oral Squamous Cell Carcinoma.

Hanan Salman Wahbi, Ahmad Al Manadili.

   OBJECTIVE: Immune checkpoint proteins, especially PD-1/PD-L1, play a vital role in controlling the intensity and duration of the immune response. However, cancer cells often over-expression PDL-1 on their surfaces, which leads to the permanent activation of the PD-1/PDL-1 pathway and exhaustion of T cells and creates a resistant tumor microenvironment. This study aimed to analyze PD-1, PD-L1 expression in tumor cells (PDL-1/TC) and in Tumor-Infiltrating Lymphocytes (PDL-1/TILS) of OSCC patients and associated with and to correlate it with histologic grade of malignancy and clinicopathologic parameters.
METHODS: The sample consisted of 43 archived specimens of 43 patients of OSCC with Clinical features (gender, age, smoking, clinical stage) collected from medical records between 2014-2021. The intensity of PD-1, PDL-1/TC, PDL-1/TILS, positive cells were assessed by immunohistochemistry.
RESULT: PDL-1/TILS and PDL-1/TC were observed in all specimens except two cases in well-differentiated were negative. PDL-1/TILS was significant between histological grades(P=0.004<0.05). There was no significant between PDL-1/TC and PDL-1/TILS and between poorly differentiated and moderately differentiated groups' ROC P values (P=0.133, 0.340>0.05) respectively. There is a difference between PDL-1/TC and PDL-1/TILS between poorly differentiated and well-differentiated groups ROC P value (0.005, 0.028), Sensitivity (0.857, 0.857), specificity (0.765, 0.824) respectively and there is a difference between and PDL-1/TILS moderate differentiated and well-differentiated groups ROC P value (0.133,) Sensitivity (0.737), specificity (0.765). No differences between PDL-1/TC and moderate and well-differentiated groups P value (0.173). There is a significant correlation between PDL-1/TC and PDL-1/TILS with an age P>65 value (0.032) in the well-differentiated group. PDL-1/TC and PDL-1/TILS with the depth of invasion (DOI) in the well-differentiated group. No significant correlation was obtained between PDL-1/TC and PDL-1/TILS and smoking, clinical stage, and gender. No significant correlation was obtained between PD1 and the histological grades or clinicopathologic characteristics.
CONCLUSION: PDL-1/TILS and PDL-1/TC are independent prognostic factors in OSCC and PDL1-/TILS has an important role.

Keywords:  immune checkpoints; programmed cell death protein 1; programmed death ligand 1; tumor-infiltrating lymphocytes

DOI:  https://doi.org/10.31557/APJCP.2024.25.10.3471
Neoplasia. 2024 Oct 24. pii: S1476-5586(24)00113-1. [Epub ahead of print]58 101072

Systematic analysis of human colorectal cancer scRNA-seq revealed limited pro-tumoral IL-17 production potential in gamma delta T cells.

Ran Ran, Martin Trapecar, Douglas K Brubaker.

  Gamma delta T cells play a crucial role in anti-tumor immunity due to their cytotoxic properties. However, the role and extent of γδ T cells in production of pro-tumorigenic interleukin-17 (IL-17) within the tumor microenvironment of colorectal cancer (CRC) remains controversial. In this study, we re-analyzed nine published human CRC whole-tissue single-cell RNA sequencing datasets, identifying 18,483 γδ T cells out of 951,785 total cells, in the neoplastic or adjacent normal tissue of 165 human CRC patients. Our results confirm that tumor-infiltrating γδ T cells exhibit high cytotoxicity-related transcription in both tumor and adjacent normal tissues, but critically, none of the γδ T cell clusters showed IL-17 production potential. We also identified various γδ T cell subsets, including poised effector-like T cells, tissue-resident memory T cells, progenitor exhausted-like T cells, and exhausted T cells, and noted an increased expression of cytotoxic molecules in tumor-infiltrating γδ T cells compared to their normal area counterparts. We proposed anti-tumor γδ T effector cells may arise from tissue-resident progenitor cells based on the trajectory analysis. Our work demonstrates that γδ T cells in CRC primarily function as cytotoxic effector cells rather than IL-17 producers, mitigating the concerns about their potential pro-tumorigenic roles in CRC, highlighting the importance of accurately characterizing these cells for cancer immunotherapy research and the unneglectable cross-species discrepancy between the mouse and human immune system in the study of cancer immunology.

Keywords:  Colorectal cancer; Gamma delta T cells; Single-cell transcriptomics

DOI:  https://doi.org/10.1016/j.neo.2024.101072
Int J Rheum Dis. 2024 Nov;27(11): e15381

The recent progress of γδ T cells and its targeted therapies in rheumatoid arthritis.

Xue Feng, Yan Xu.

  Rheumatoid arthritis (RA) is an autoimmune condition that mostly impacts the joints. During the advanced phases of the disorder, it may be accompanied by other problems. While the precise cause of RA is uncertain, various research has been conducted to gain a better understanding of the immunological processes involved in the development of RA. T cells are acknowledged as significant contributors to the progression of RA because of their roles in cytokine secretion, antigen presentation, and facilitating B cells in the manufacture of antibodies. γδ T cells are a small subset of T cells that have significant functions in the context of infection and diseases linked with tumors. γδ T cells have been the subject of investigation in autoimmune disorders in recent years. This review focused on the involvement of γδ T lymphocytes in the development of RA. In this article, we provide an analysis of the immunological capabilities of γδ T cells, intending to comprehend their significance in RA, which could be pivotal in the creation of innovative clinical treatments.

Keywords:  T cell; lymphocyte; rheumatic disease; rheumatoid arthritis; γδ T cells

DOI:  https://doi.org/10.1111/1756-185X.15381
World J Clin Oncol. 2024 Oct 24. 15(10): 1280-1292

Comprehensive assessment of the association between tumor-infiltrating immune cells and the prognosis of renal cell carcinoma.

Guo-Hao Wei, Xi-Yi Wei, Ling-Yao Fan, Wen-Zheng Zhou, Ming Sun, Chuan-Dong Zhu.

   BACKGROUND: According to current statistics, renal cancer accounts for 3% of all cancers worldwide. Renal cell carcinoma (RCC) is the most common solid lesion in the kidney and accounts for approximately 90% of all renal malignancies. Increasing evidence has shown an association between immune infiltration in RCC and clinical outcomes. To discover possible targets for the immune system, we investigated the link between tumor-infiltrating immune cells (TIICs) and the prognosis of RCC.
AIM: To investigate the effects of 22 TIICs on the prognosis of RCC patients and identify potential therapeutic targets for RCC immunotherapy.
METHODS: The CIBERSORT algorithm partitioned the 22 TIICs from the Cancer Genome Atlas cohort into proportions. Cox regression analysis was employed to evaluate the impact of 22 TIICs on the probability of developing RCC. A predictive model for immunological risk was developed by analyzing the statistical relationship between the subpopulations of TIICs and survival outcomes. Furthermore, multivariate Cox regression analysis was used to investigate independent factors for the prognostic prediction of RCC. A value of P < 0.05 was regarded as statistically significant.
RESULTS: Compared to normal tissues, RCC tissues exhibited a distinct infiltration of immune cells. An immune risk score model was established and univariate Cox regression analysis revealed a significant association between four immune cell types and the survival risk connected to RCC. High-risk individuals were correlated to poorer outcomes according to the Kaplan-Meier survival curve (P = 1E-05). The immunological risk score model was demonstrated to be a dependable predictor of survival risk (area under the curve = 0.747) via the receiver operating characteristic curve. According to multivariate Cox regression analysis, the immune risk score model independently predicted RCC patients' prognosis (hazard ratio = 1.550, 95%CI: 1.342-1.791; P < 0.001). Finally, we established a nomogram that accurately and comprehensively forecast the survival of patients with RCC.
CONCLUSION: TIICs play various roles in RCC prognosis. The immunological risk score is an independent predictor of poor survival in kidney cancer cases.

Keywords:  Immune risk score model; Nomogram; Prognosis; Renal cell carcinoma; Tumor-infiltrating immune cells

DOI:  https://doi.org/10.5306/wjco.v15.i10.1280