Influence of chemoradiation on the immune microenvironment of cervical cancer patients.

PURPOSE: Cervical cancer remains a leading cause of cancer death in women. While immunotherapy has shown great success in combating cancer, the value of immunotherapy in cervical cancer is still only beginning to be explored. Thus, we performed a prospective analysis of patient blood and tumor samples at the beginning and end of conventional chemoradiation to assess changes in the immune cell and immunoreceptor compartments, and investigate if and when the addition of immunotherapy could be beneficial. METHODS: Patients with FIGO II-III cervical cancer receiving standard chemoradiation between January 2020 and December 2021 were included. We collected tumor and blood samples from patients before and at the end of therapy and analyzed immune cell composition and immune checkpoint receptor expression on both immune and tumor cells using multicolor flow cytometry. RESULTS: In all, 34 patients were eligible in the study period; 22 could be included and analyzed in this study. We found that chemoradiation significantly reduces T cell numbers in both tumors and blood, but increases macrophage and neutrophil numbers in tumors. Furthermore, we found that the percentage of immune checkpoint receptor PD­1 and TIGIT-expressing cells in tumors was significantly reduced at the end of therapy and that CD4 and CD8 memory T cell populations were altered by chemoradiation. In addition, we observed that while PD-L1 expression intensity was upregulated by chemoradiation on blood CD8 cells, PD-L1 expression frequency and the expression intensity of antigen-presenting molecule MHC­I were significantly reduced on tumor cells. CONCLUSION: Our data demonstrate that chemoradiation significantly alters the immune cell composition of human cervical tumors and the expression of immune checkpoint receptors on both lymphocytes and tumor cells. As our results reveal that the percentage of PD­1+ CD8 cells in the tumor as well as the frequency of PD-L1-expressing tumor cells were reduced at the end of therapy, neoadjuvant or simultaneous anti-PD­1 or anti-PD-L1 treatment might provide better treatment efficiency in upcoming clinical studies.

Evolution of adjuvant treatment in endometrial cancer-no evidence and new questions?

PURPOSE: For endometrial cancer (EC), clinical and pathological risk factors are taken to triage patients and estimate their prognosis. Lymph node involvement (pN+), lymphovascular space involvement (LSVI), grading, age of the patients, and T classification are internationally accepted parameters for treatment decisions. MATERIALS AND METHODS: Studies on adjuvant radiation, chemotherapy, and chemoradiation are discussed against the background of risk stratification and clinical decision-making in early-to-advanced stage endometrial cancer. Recent publications on adjuvant treatment in high-risk disease and its implications for the patients with regard to expected oncologic benefit and treatment-related toxicity are discussed. RESULTS: Surgery is the mainstay of treatment of EC patients. Well-differentiated tumors and early disease (FIGO IA) should be followed up without further treatment. In FIGO I stage without risk factors, VBT remains the standard treatment after surgery. FIGO I, II patients with one or more risk factors (MI ≥ 50%, Grading[G]3, age >60 years, LVSI) benefit from external beam radiotherapy (EBRT) in terms of survival. There are no data of acceptable quality demonstrating that chemotherapy is superior to radiation in locally advanced carcinomas. Therefore, even in locally advanced disease (FIGO III, IV), EBRT remains the standard of care after surgery. EBRT contributes to the very low rate of local relapses and better DFS in these patients and should not be replaced by chemotherapy only. Whether and which subgroups of patients benefit from an additional (concomitant and/or adjuvant) chemotherapy in terms of disease-free survival remains a controversial issue. The recently published PORTEC-3 trial could not create clear evidence. With a high rate of isolated tumors cells and micrometastases in the specimens, the increasing use of unvalidated sentinel concepts in endometrial cancer raises more questions with regard to indications for adjuvant treatment. In the future, integrated genomic characterization of tumors might be helpful for treatment individualization in the adjuvant setting.

Platelets in inflammation and immunity.

The paradigm of platelets as mere mediators of hemostasis has long since been replaced by a dual role: hemostasis and inflammation. Now recognized as key players in innate and adaptive immune responses, platelets have the capacity to interact with almost all known immune cells. These platelet-immune cell interactions represent a hallmark of immunity, as they can potently enhance immune cell functions and, in some cases, even constitute a prerequisite for host defense mechanisms such as NETosis. In addition, recent studies have revealed a new role for platelets in immunity: They are ubiquitous sentinels and rapid first-line immune responders, as platelet-pathogen interactions within the vasculature appear to precede all other host defense mechanisms. Here, we discuss recent advances in our understanding of platelets as inflammatory cells, and provide an exemplary review of their role in acute inflammation.