Tim-4+ cavity-resident macrophages impair anti-tumor CD8+ T cell immunity

Ascites and resistance to immune checkpoint inhibition in dMMR/MSI-H metastatic colorectal and gastric cancers

“…15-17 22-25 Contrary to the more intuitive theory that peritoneum and pleura could represent an immune-excluded milieu because of the difficulty of immune system to penetrate the effusion fluids, recent studies supported the idea of serous cavities as an immune-enriched environment with high concentration of immune-suppressive cells such as macrophages, myeloid-derived suppressive cells and T regulatory cells. [15][16][17] Also, a recent work showed that cavity-resident Tim-4 + macrophages populate the pleural and peritoneal microenvironment and can induce an immune-suppressed microenvironment by impairing CD8 + T cells proliferation. 17 In this context, dual Tim-4/ PD-1 blockade was synergic in murine models.…”

“…[15][16][17] Also, a recent work showed that cavity-resident Tim-4 + macrophages populate the pleural and peritoneal microenvironment and can induce an immune-suppressed microenvironment by impairing CD8 + T cells proliferation. 17 In this context, dual Tim-4/ PD-1 blockade was synergic in murine models. 17 In attempt to clinically validate these results, the authors analyzed a monocentre cohort of 61 patients with MSIhigh mCRC treated with ICIs, reporting worse outcomes in those with peritoneal metastases, with unadjusted HRs for PFS and OS of 2.69 and 3.59, respectively.…”

“…17 In this context, dual Tim-4/ PD-1 blockade was synergic in murine models. 17 In attempt to clinically validate these results, the authors analyzed a monocentre cohort of 61 patients with MSIhigh mCRC treated with ICIs, reporting worse outcomes in those with peritoneal metastases, with unadjusted HRs for PFS and OS of 2.69 and 3.59, respectively. However, given the relatively low prevalence of ascites in their cohort of mCRC, it was not possible to investigate the prognostic impact of peritoneal metastases in a multivariable model and according to the presence or absence of malignant effusion.…”

“…15 16 Indeed, serous cavities are an immunologic niche due to a variety of immunosuppressive networks, such as those driven by cavity-resident macrophages with Tim-4 overexpression. 17 Drawing from these considerations, we hypothesized that patients with MSI-H cancers and coexisting malignant ascites may have poorer outcomes and high rates of primary resistance to ICI treatment. To examine this hypothesis, we assembled a large multinational cohort of patients with dMMR/ MSI-H mCRC or GC receiving ICIs to investigate the prognostic role of peritoneal involvement with or without ascites.…”

Pembrolizumab monotherapy versus pembrolizumab plus chemotherapy in patients with non‐small‐cell lung cancer: A multicenter retrospective trial

“…There were fewer patients with a high PD‐L1 expression in the combination therapy group; this may have resulted in no difference in PFS and OS (Figure 1a,c,d ) in the overall population. Some metastasis‐specific prognostic factors, such as Royal Marsden Hospital scores and Gustave Roussy Immune scores in liver metastasis, 27 and Tim‐4 positive cavity‐resident macrophages in malignant pleural effusion, 28 were not analyzed in this study. Therefore, further studies with a larger sample size and prospective design are required to validate the findings from our study, especially in the area of immunological translational research.…”