The Emerging Role of CD8+ Tissue Resident Memory T (TRM) Cells in Antitumor Immunity: A Unique Functional Contribution of the CD103 Integrin

Cancer immunotherapy is aimed at stimulating tumor-specific cytotoxic T lymphocytes and their subsequent trafficking so that they may reach, and persist in, the tumor microenvironment, recognizing and eliminating malignant target cells. Thus, characterization of the phenotype and effector functions of CD8+ T lymphocytes infiltrating human solid tumors is essential for better understanding and manipulating the local antitumor immune response, and for defining their contribution to the success of current cancer immunotherapy approaches. Accumulating evidence indicates that a substantial subpopulation of CD3+CD8+ tumor-infiltrating lymphocytes are tissue resident memory T (TRM) cells, and is emerging as an activated tumor-specific T-cell subset. These TRM cells accumulate in various human cancer tissues, including non-small-cell lung carcinoma (NSCLC), ovarian and breast cancers, and are defined by expression of CD103 [αE(CD103)β7] and/or CD49a [α1(CD49a)β1] integrins, along with C-type lectin CD69, which most likely contribute to their residency characteristic. CD103 binds to the epithelial cell marker E-cadherin, thereby promoting retention of TRM cells in epithelial tumor islets and maturation of cytotoxic immune synapse with specific cancer cells, resulting in T-cell receptor (TCR)-dependent target cell killing. Moreover, CD103 integrin triggers bidirectional signaling events that cooperate with TCR signals to enable T-cell migration and optimal cytokine production. Remarkably, TRM cells infiltrating human NSCLC tumors also express inhibitory receptors such as programmed cell death-1, the neutralization of which, with blocking antibodies, enhances CD103-dependent TCR-mediated cytotoxicity toward autologous cancer cells. Thus, accumulation of TRM cells at the tumor site explains the more favorable clinical outcome, and might be associated with the success of immune checkpoint blockade in a fraction of cancer patients

Activity of EGFR Tyrosine Kinase Inhibitors in NSCLC With Refractory Leptomeningeal Metastases

International audienc

Real-life clinical management patterns in extensive-stage small cell lung cancer across France: a multi-method study

Abstract Background We designed this study based on both a physician practice survey and real-world patient data to: (1) evaluate clinical management practices in extensive-stage small cell lung cancer (ES-SCLC) among medical centers located across France; and (2) describe first-line treatment patterns among patients with ES-SCLC following the introduction of immunotherapy into clinical practice. Methods A 50-item questionnaire was completed by physicians from 45 medical centers specialized in SCLC management. Responses were collected from June 2022 to January 2023. The survey questions addressed diagnostic workup of ES-SCLC, chemoimmunotherapy in first-line and second-line settings, and use of prophylactic cranial irradiation (PCI) and radiotherapy. In parallel, using a chart review approach, we retrospectively analyzed aggregated information from 548 adults with confirmed ES-SCLC receiving first-line treatment in the same centers. Results In ES-SCLC, treatment planning is based on chest computed tomography (CT) (as declared by 100% of surveyed centers). Mean time between diagnosis and treatment initiation was 2–7 days, as declared by 82% of centers. For detection of brain metastases, the most common imaging test was brain CT (84%). The main exclusion criteria for first-line immunotherapy in the centers were autoimmune disease (87%), corticosteroid therapy (69%), interstitial lung disease (69%), and performance status ≥ 2 (69%). Overall, 53% and 36% of centers considered that patients are chemotherapy-sensitive if they relapse within ≥ 3 months or ≥ 6 months after first-line chemoimmunotherapy, respectively. Among the 548 analyzed patients, 409 (75%) received chemoimmunotherapy as a first-line treatment, 374 (91%) of whom received carboplatin plus etoposide and 35 (9%) cisplatin plus etoposide. Overall, 340/548 patients (62%) received maintenance immunotherapy. Most patients (68%) did not receive radiotherapy or PCI. Conclusions There is an overall alignment of practices reflecting recent clinical guidelines among medical centers managing ES-SCLC across France, and a high prescription rate of immunotherapy in the first-line setting

Evaluation of Real-Life Chemoimmunotherapy Combination in Patients with Metastatic Small Cell Lung Carcinoma (SCLC): A Multicentric Case–Control Study

The current first-line standard treatment for advanced small cell lung cancer (SCLC) is a combination of chemotherapy and immunotherapy. However, few efficacy data are available in a real-life settings, including frail patients. The aim of this study is to describe the real-life efficacy of chemoimmunotherapy in an unselected SCLC population. We conducted a retrospective multicenter study, which compared two cohorts of patients with treatment-naive metastatic SCLC treated in six academic centers in the Greater Paris area. Cohort 1 included patients treated with chemotherapy between January 2017 and December 2018, and cohort 2 included patients treated with chemoimmunotherapy between January 2019 and December 2020. A total of 153 consecutive patients were included (cohort 1: n = 96; cohort 2: n = 57). Clinical characteristics were similar between the two cohorts. Overall survival (OS) was statistically higher in cohort 2 (median survival 15.47 months) than in cohort 1 (median survival 9.5 months) (p = 0.0001). OS for patients with a performance status ≥2 and for patients ≥70 years old was not statistically different between the two cohorts. Chemoimmunotherapy efficacy was better compared to chemotherapy alone in case of brain or liver metastases. In conclusion, the combination of chemoimmunotherapy in metastatic SCLC appears to provide a real-life OS benefit. Dedicated clinical trials are needed to test this strategy in patients with impaired performance status or advanced age

Additional file 1 of Real-life clinical management patterns in extensive-stage small cell lung cancer across France: a multi-method study

Supplementary Material 1: Data Collection Tool

Outcomes of extended resection for locally advanced thymic malignancies

International audienc

Long-term effectiveness and treatment sequences in patients with extensive stage small cell lung cancer receiving atezolizumab plus chemotherapy: Results of the IFCT-1905 CLINATEZO real-world study

International audienceBackground: Small cell lung cancer (SCLC) has a tendency towards recurrence and limited survival. Standard-of-care in 1st-line is platinum-etoposide chemotherapy plus atezolizumab or durvalumab, based on landmark clinical trials. Methods: IFCT-1905 CLINATEZO is a nationwide, non-interventional, retrospective study of patients with extensive-SCLC receiving atezolizumab plus chemotherapy as part of French Early Access Program. Objectives were to analyse effectiveness, safety and subsequent treatments. Results: The population analyzed included 518 patients who received atezolizumab in 65 participating centers. There were 66.2% male, mean age was 65.7 years; 89.1% had a performance status (PS) 0/1 and 26.6% brain metastases. Almost all (95.9%) were smokers. Fifty-five (10.6%) received at least 1 previous treatment. Median number of atezolizumab injections was 7.0 (range [1.0–48.0]) for a median duration of 4.9 months (95% CI 4.5–5.1). Atezolizumab was continued beyond progression in 122 patients (23.6%) for a median duration of 1.9 months (95% CI: [1.4–2.3]). Best objective response was complete and partial in 19 (3.9%) and 378 (77.1%) patients. Stable disease was observed in 50 patients (10.2%). Median follow-up was 30.8 months (95% CI: [29.9–31.5]). Median overall survival (OS), 12-, 24-month OS rates were 11.3 months (95% CI: [10.1–12.4]), 46.7% (95% CI [42.3–50.9]) and 21.2% (95% CI [17.7–24.8]). Median real-world progression-free survival, 6-, 12-month rates were 5.2 months (95% CI [5.0–5.4]), 37.5% (95% CI [33.3–41.7]) and 15.2% (95% CI [12.2–18.6]). For patients with PS 0/1, median OS was 12.2 months (95% CI [11.0–13.5]). For patients with previous treatment, median OS was 14.9 months (95% CI [10.1–21.5]). Three-hundred-and-twenty-six patients (66.4%) received subsequent treatment and 27 (5.2%) were still under atezolizumab at date of last news. Conclusions: IFCT-1905 CLINATEZO shows reproductibility, in real-life, of IMpower-133 survival outcomes, possibly attributed to selection of patients fit for this regimen, adoption of pragmatic approaches, including concurrent radiotherapy and treatment beyond progression

The Clinical Utility of Liquid Biopsy by Digital Droplet PCR in Patients with Advanced NSCLC [P34.06]

INTRODUCTION : EGFR mutations occur in 15% of Caucasian and up to 50% of Asian patients with advanced NSCLC. Tissue genomic profiling is the gold standard but the liquid biopsy is a good surrogate of the tissue for molecular diagnosis. The digital droplet PCR (ddPCR) is a rapid and low-cost liquid biopsy technique for genomic analyses. We aimed to evaluate the clinical utility of the ddPCR for genomic profiling of advanced NSCLC with EGFR mutations. [...