TILs and Anti-PD1 Therapy: An Alternative Combination Therapy for PDL1 Negative Metastatic Cervical Cancer

Yin, Huanhuan; Guo, Wei; Sun, Xiangling; Li, Ruili; Feng, Cuihua; Tan, Yongtao

doi:10.1155/2020/8345235

Cited by 32 publications

(31 citation statements)

References 37 publications

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“…25,26 Recent studies have reported that combining anti-PD1 with TIL therapy may confer more effective antitumour effects on metastatic cervical cancer (SCC cases = 65; adenocarcinoma cases = 15). 27 The NLR probably represents the activity of myeloid-derived suppressor cells, which hinder T cell proliferation. 28 The usefulness of NLR as a prognostic biomarker in patients with various solid tumours who received immune checkpoint inhibitors has been investigated.…”

Section: Discussionmentioning

confidence: 99%

PD‐L1 expression and immune stromal features in HPV‐independent cervical adenocarcinoma

Song

Meng

et al. 2021

Histopathology

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Human papilloma virus (HPV)-independent cervical adenocarcinoma (CA) is usually diagnosed at an advanced stage, while the therapeutic options are limited. Therefore, effective treatment options are required. The programmed cell death 1 (PD-1) inhibitor pembrolizumab has been approved for the treatment of patients with recurrent or metastatic cervical squamous cell carcinoma expressing PD-ligand 1 (PD-L1). However, no data regarding PD-L1 expression in HPV-independent CA are available. Thus, we evaluated the association between PD-L1 expression and the clinicopathological characteristics and survival of patients with HPV-independent CA. Methods: We evaluated PD-L1, mismatch repair (MMR) protein expression and the immune stromal features of 44 patients with HPV-independent CA. PD-L1 expression was defined as a combined positive score (CPS) ≥1 and a tumour proportion score (TPS) ≥1%.Results: PD-L1 expression was observed in 14 cases (31.8%) with CPS ≥1 and 12 cases (27.3%) with TPS ≥1%. PD-L1 expression, based on either the CPS or the TPS, was associated with a high tumourinfiltrating lymphocyte percentage (CPS = P < 0.001; TPS = P < 0.001). Patients with a PD-L1 CPS ≥1 showed worse progression-free survival and overall survival than PD-L1-negative patients (P = 0.004 and P = 0.023, respectively). Forty-two cases demonstrated intact MMR expression and two cases demonstrated loss of MSH2/MSH6. Conclusions: Our data demonstrated that PD-L1 was expressed in HPV-independent CA, especially in clear cell carcinoma, and that PD-L1 expression is a negative prognostic marker. Our data support the role of PD-L1 in HPV-independent CA and its potential as an immunotherapeutic target.

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Section: Discussionmentioning

confidence: 99%

PD‐L1 expression and immune stromal features in HPV‐independent cervical adenocarcinoma

Song

Meng

et al. 2021

Histopathology

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“…Similar to ICB, TIL ACT tends to be effective against tumors containing viral antigens. It has been reported that patients with HPV-positive metastatic cervical cancer were significantly more likely to respond to TIL ACT as compared to HPV-negative patients (129). In another study, three out of nine cervical cancer patients responded to treatment with TILs that were pre-selected for reactivity to HPV (136).…”

Section: Viral Infectionsmentioning

confidence: 90%

Cell Therapy With TILs: Training and Taming T Cells to Fight Cancer

2021

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The rationale behind cancer immunotherapy is based on the unequivocal demonstration that the immune system plays an important role in limiting cancer initiation and progression. Adoptive cell therapy (ACT) is a form of cancer immunotherapy that utilizes a patient’s own immune cells to find and eliminate tumor cells, however, donor immune cells can also be employed in some cases. Here, we focus on T lymphocyte (T cell)-based cancer immunotherapies that have gained significant attention after initial discoveries that graft-versus-tumor responses were mediated by T cells. Accumulating knowledge of T cell development and function coupled with advancements in genetics and data science has enabled the use of a patient’s own (autologous) T cells for ACT (TIL ACTs). In TIL ACT, tumor-infiltrating lymphocytes (TILs) are collected from resected tumor material, enhanced and expanded ex-vivo, and delivered back to the patient as therapeutic agents. ACT with TILs has been shown to cause objective tumor regression in several types of cancers including melanoma, cervical squamous cell carcinoma, and cholangiocarcinoma. In this review, we provide a brief history of TIL ACT and discuss the current state of TIL ACT clinical development in solid tumors. We also discuss the niche of TIL ACT in the current cancer therapy landscape and potential strategies for patient selection.

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“…TILs are associated with a significantly positive clinical outcome in cervical cancer. They have been identified for tumor specificity, extracted from resected tumor tissue and proliferated ex vivo in media containing cytokines [47,48]. Adoptive T cells have been observed to induce tumor regression at a greater rate than vaccinated lymphocytes [49,50].…”

Section: Adoptive T-cell Therapymentioning

confidence: 99%

“…These modified receptors are capable of recognizing specific MHC antigens [52]. Hence, T-cell receptor therapy involves selecting and targeting specific intracellular and extracellular antigens by modified T-cell receptors, in contrast to TIL therapy, where endogenous tumor-directed lymphocytes are chosen [48]. The modified receptor cells are reinfused into patients, where they induce tumor cell lysis through cytokine production.…”

Section: Genetic Modification Of T Cellsmentioning

confidence: 99%

Nanomedicine-Mediated Optimization of Immunotherapeutic Approaches in Cervical Cancer

Venkatas

Singh

2021

Nanomedicine (Lond.)

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Cervical cancer shows immense complexity at the epigenetic, genetic and cellular levels, limiting conventional treatment. Immunotherapy has revolutionized nanomedicine and rejuvenated the field of tumor immunology. Although several immunotherapeutic approaches have shown favorable clinical responses, their efficacies vary, with subsets of patients benefitting. The success of cancer immunotherapy requires the enhancement of cytokines and antitumor effector cell production and activation. Recently, the feasibility of nanoparticle-based cytokine approaches in tumor immunotherapy has been highlighted. Immunotherapeutic nanoparticle-based platforms form a novel strategy enabling researchers to co-deliver immunomodulatory agents, target tumors, improve pharmacokinetics and minimize collateral toxicity to healthy cells. This review looks at the potential of immunotherapy and nanotechnologically enhanced immunotherapeutic approaches for cervical cancer.

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TILs and Anti-PD1 Therapy: An Alternative Combination Therapy for PDL1 Negative Metastatic Cervical Cancer

Cited by 32 publications

References 37 publications

PD‐L1 expression and immune stromal features in HPV‐independent cervical adenocarcinoma

PD‐L1 expression and immune stromal features in HPV‐independent cervical adenocarcinoma

Cell Therapy With TILs: Training and Taming T Cells to Fight Cancer

Nanomedicine-Mediated Optimization of Immunotherapeutic Approaches in Cervical Cancer

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