From Tumor Immunosuppression to Eradication: Targeting Homing and Activity of Immune Effector Cells to Tumors

Unraveling the mechanisms used by the immune system to fight cancer development is one of the most ambitious undertakings in immunology. Detailed knowledge regarding the mechanisms of induction of tolerance and immunosuppression within the tumor microenvironment will contribute to the development of highly effective tumor eradication strategies. Research within the last few decades has shed more light on the matter. This paper aims to give an overview on the current knowledge of the main tolerance and immunosuppression mechanisms elicited within the tumor microenvironment, with the focus on development of effective immunotherapeutic strategies to improve homing and activity of immune effector cells to tumors

Tumor-infiltrating lymphocytes in the immunotherapy era

The clinical success of cancer immune checkpoint blockade (ICB) has refocused attention on tumor-infiltrating lymphocytes (TILs) across cancer types. The outcome of immune checkpoint inhibitor therapy in cancer patients has been linked to the quality and magnitude of T cell, NK cell, and more recently, B cell responses within the tumor microenvironment. State-of-the-art single-cell analysis of TIL gene expression profiles and clonality has revealed a remarkable degree of cellular heterogeneity and distinct patterns of immune activation and exhaustion. Many of these states are conserved across tumor types, in line with the broad responses observed clinically. Despite this homology, not all cancer types with similar TIL landscapes respond similarly to immunotherapy, highlighting the complexity of the underlying tumor-immune interactions. This observation is further confounded by the strong prognostic benefit of TILs observed for tumor types that have so far respond poorly to immunotherapy. Thus, while a holistic view of lymphocyte infiltration and dysfunction on a single-cell level is emerging, the search for response and prognostic biomarkers is just beginning. Within this review, we discuss recent advances in the understanding of TIL biology, their prognostic benefit, and their predictive value for therapy

Incidence of gynaecological cancer during the COVID-19 pandemic:A population-based study in the Netherlands

Objective: To study the impact of the COVID-19 pandemic and consequent lockdown on the number of diagnoses of gynaecological malignancies in the Netherlands. Methods: We performed a retrospective cohort study using data from the Netherlands Cancer Registry (NCR) on women of 18 years and older diagnosed with invasive endometrial, ovarian, cervical or vulvar cancer in the period 2017–2021. Analyses were stratified for age, socioeconomical status (SES) and region. Results: The incidence rate of gynaecological cancer was 67/100.000 (n = 4832) before (2017–2019) and 68/100.000 (n = 4833) during (2020) the COVID-19 pandemic. Comparing the number of diagnoses of the two periods for the four types of cancer separately showed no significant difference. During the first wave of COVID-19 (March-June 2020), a clear decrease in number of gynaecological cancer diagnoses was visible (20–34 %). Subsequently, large increases in number of diagnoses were visible (11–29 %). No significant differences in incidence were found between different age groups, SES and regions. In 2021 an increase of 5.9 % in number of diagnoses was seen. Conclusion: In the Netherlands, a clear drop in number of diagnoses was visible for all four types of gynaecological cancers during the first wave, with a subsequent increase in number of diagnoses in the second part of 2020 and in 2021. No differences between SES groups were found. This illustrates good organisation of and access to health care in the Netherlands.</p

End-of-life care for patients with advanced ovarian cancer in the Netherlands:A retrospective registry-based analysis

OBJECTIVE: Patients with advanced ovarian cancer have a poor prognosis and can experience debilitating symptoms in the last phase of life. Several analyses, mainly performed in the United States (US), show high rates of chemotherapy administration and hospital visits near the end-of-life in this patient category. No large European studies are available, while the organisation of palliative care differs between the US and Europe. We aimed to analyse the intensity of inpatient care near the end-of-life in the Netherlands and perform a cross-study comparison with previous reports. METHODS: All patients with ovarian cancer that died in 2016 and 2017 were identified from the Vektis database, a data warehouse including all insurance declarations in the Netherlands. For the last 6 months of life the following parameters of aggressive care were extracted: administration of chemotherapy, emergency room (ER) visits, surgical procedures, hospital and intensive care unit (ICU) admissions. The intensity of inpatient care was compared to previously reported European and US data. RESULTS: Data on medical care use was available for 1775 patients. During the last 6 months of life, half of the ovarian cancer patients were admitted to hospital. Chemotherapy administration near the end-of-life was infrequent: 12% in the last month of life. Surgery and ICU admissions in the final 6 months of life were rare (<10%). Our cohort showed the lowest percentages of all five indicators of aggressive care reported thus far. CONCLUSION: Aggressive medical care use in the final 6 months of life in this Dutch cohort of ovarian cancer patients was lower than in other previously reported cohorts