Introduction: Resistance to immune checkpoint inhibitors (ICI) is a significant issue in metastatic renal cell carcinoma (mRCC), as it is in the majority of cancer types. An important deficiency in immunooncology today is the lack of a predictive factor to identify this patient group. Myeloid-derived suppressor cells (MDSC) are a type of cell that contributes to immunotherapy resistance by inhibiting T cell activity. While it accumulates in the tumor microenvironment and blood, it can also accumulate in lymphoid organs such as the spleen and cause splenomegaly. Therefore we aimed to evaluate the effect of increase in splenic volume, which can be considered as an indirect indicator of increased MDSC cells, on survival outcomes in mRCC patients. Methods: We analyzed 45 patients with mRCC who received nivolumab as a second-line or subsequent therapy. Splenic volume was analyzed from baseline imaging before starting nivolumab and from control imaging performed within the first 6 months of treatment initiation. Additionally, we analyzed how patients’ body mass index (BMI), IMDC risk score, ECOG performance status, nephrectomy status, neutrophil-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR) and sites of metastasis. Results: Median splenic volume change was 10% (ranging from − 22% to + 117%) during follow-up. Change in splenic volume was found to be associated with overall survival (OS) and progression-free survival (PFS) (p = 0.025, 0.04). The median PFS in patients with increased splenic volume was 5 months, while it was 17 months in patients without increased splenic volume. (HR 2.1, 95% CI (1–4), p = 0.04). The median OS in patients with increased splenic volume was 9 months, while it was 35 months in patients without increased splenic volume (HR 2.7, 95% CI (1.1–6.2), p = 0.025). In four patients with decreased splenic volume, neither PFS nor OS could reach the median value. Log-rank p value in respectively (0.015, 0.035), The group in which an increase in volume was accompanied by a high NLR had the shortest survival rate. Basal splenic volume was analyzed separately. However, neither PFS nor OS differed significantly. Conclusion: Our findings suggest that the change in splenic volume throughout immunotherapy regimens may be utilized to predict PFS and OS in mRCC patients undergoing treatment.

Introduction Immune checkpoint inhibitors (ICIs) targeting PD-1 and PD-L1 have emerged as promising treatments for advanced NSCLC patients without actionable mutations. However, predicting treatment response remains challenging, especially in second-line settings. Although PD-L1 is the only validated biomarker, additional prognostic tools are needed. Systemic inflammation markers such as the neutrophil-to-lymphocyte ratio (NLR) show potential but remain underused. Myeloid-derived suppressor cells (MDSCs), linked to immunotherapy resistance, are associated with increased splenic volume. Therefore this study introduces a splenic index score, combining pre-immunotherapy splenic volume and NLR, to evaluate its prognostic value in NSCLC patients treated with nivolumab in the second-line setting. We analyzed 50 patients with metastatic non-small cell lung cancer (NSCLC) who received nivolumab as second-line or later therapy. Baseline splenic volume and neutrophil-to-lymphocyte ratio (NLR) were assessed using imaging and laboratory data prior to nivolumab initiation. The Splenic Index Score for each patient was calculated using the formula: (baseline splenic volume) × (NLR). Additionally, we evaluated the impact of other factors, including body mass index (BMI), tumor PD-L1 expression, Eastern Cooperative Oncology Group (ECOG) performance status, and sites of metastasis. The median Splenic Index score was 877.3 (range: 180–4830). A higher Splenic Index score was significantly associated with worse overall survival (OS) and progression-free survival (PFS) (p = 0.001 and p = 0.03, respectively). Specifically, patients with a high Splenic Index score had a median PFS of 3 months, compared to 8 months in those with a low Splenic Index score (HR 1.96, 95% CI 1-3.7, p = 0.03). Similarly, the median OS was 4 months for patients with a high Splenic Index score, while it was 15 months for those with a low score (HR 3.5, 95% CI 1.6–7.3, p = 0.001). Baseline splenic volume, basal NLR, and tumor PD-L1 expression were also evaluated; however, no significant differences in PFS or OS were observed for these parameters. Our study demonstrates that the splenic index score, derived from combining radiological and peripheral inflammatory biomarkers, serves as a predictive tool for progression-free survival (PFS) and overall survival (OS) in metastatic NSCLC patients receiving second-line nivolumab therapy.

Supportive agents, such as vitamin B12 (cobalamin, B12) and granulocyte colony-stimulating factor (G-CSF), are widely used during chemotherapy; however, their direct effects on tumor biology are not well understood. We evaluated the impact of pharmacological B12 and G-CSF, alone or in combination with cisplatin, on hormone receptor-positive (MCF-7) and triple-negative (MDA-MB-231) breast cancer cells, conducting in vitro assays of cell viability, cytotoxicity, caspase activation, mitochondrial membrane potential, and cytolytic protein expression. Neither B12 nor G-CSF alone induced cytotoxicity; instead, both promoted proliferation in a dose- and time-dependent manner. When combined with cisplatin, they consistently attenuated drug-induced cytotoxicity, suppressed caspase-3/-8/-9 activation, preserved mitochondrial integrity, and reduced perforin/granzyme expression, exhibiting stronger effects in MCF-7 cells. G-CSF markedly increased proliferation (>130% at 50 ng/mL), while B12 modestly enhanced viability and mitigated cisplatin-induced damage, particularly in triple-negative cells. These findings indicate that B12 and G-CSF can impair cisplatin efficacy by blunting apoptotic signaling and mitochondrial injury in different breast cancer subtypes. These preclinical findings warrant prospective, biomarker-driven in vivo and clinical studies to delineate the clinical contexts in which B12 and G-CSF can be safely integrated into supportive care without compromising antitumor efficacy.

To the Editor In their cohort study, Ricciuti et al¹ found that increasing tumor mutation burden (TMB) levels were associated with immune cell infiltration and an inflammatory T-cell–mediated response, resulting in increased sensitivity to programmed cell death–1 (PD-1) or PD-1 ligand (PD-L1) blockade. In subgroup analysis, high TMB compared with low TMB was associated with higher response rates and survival outcomes in each PD-L1 subset. Especially in the group with PD-L1 50% and above, the best results were observed.¹ We have some concerns about the interpretation of the study results in oncology practice.