Lymphoma refers to a group of heterogeneous malignancies originating from the reticuloendothelial and lymphatic systems. The clinical manifestations, treatment strategies, and disease outcomes of different types of lymphoma considerably vary. Recent developments in high-throughput sequencing technologies have enhanced understanding of the pathogenesis and molecular stratification of lymphoma. In the era of new drugs, precise stratification and targeted drug selection can not only improve the prognosis of patients with lymphoma but also reduce the toxic side effects of traditional chemotherapy, ultimately achieving the accurate diagnosis and individualized treatment of tumors. This article reviews the research progress of molecular diagnosis and individualized treatment of different lymphoma subtypes and lymphoma-related research in important meetings such as ASCO, EHA, and ICML in 2023.

Objective:To screen and analyze the prognostic protein biomarkers of DLBCL, and to explore their value in the prognostic evaluation.Methods:163 cases of confirmed DLBCLs from January 2011 to December 2016 were collected with their clinical, pathological and follow-up data, which were all from our hospital. The expression of protein markers were tested using immunohistochemical staining (IHC) . The immune phenotypes independent of the International Prognostic Index (IPI) that affect overall survival (OS) and progression-free survival (PFS) of DLBCL were explored by COX regression model, and the effect of their co-expression on the prognosis were also analyzed.Result:BCL6 negative (PFS: HR=1.652, 95% CI 1.030-2.649, P=0.037) , P53 positive (OS: HR=1.842, 95% CI 1.008-3.367, P=0.047) , and BCL2 strong positive expressions (S+) (OS: HR=2.102, 95% CI 1.249-3.537, P=0.005; PFS: HR=2.126, 95% CI 1.312-3.443, P=0.002) are adverse prognostic factors of DLBCL that are independent of IPI. BCL6 - (PFS: HR=2.042, 95% CI 1.021-4.081, P=0.043) , P53 + (OS: HR=3.069, 95% CI 1.244-7.569, P=0.015) and BCL2 S+ (OS: HR=2.433, 95% CI 1.165-5.082, P=0.018; PFS: HR=3.209, 95% CI 1.606-6.410, P=0.001) are adverse prognostic factors in the group of age≤60-year-old; in the group of IPI score 0-2, cases with BCL6 - (OS: HR=2.467, 95% CI 1.322-4.604, P=0.005; PFS: HR=2.248, 95% CI 1.275-3.965, P=0.005) and BCL2 S+ (PFS: HR=2.045, 95% CI 1.119-3.735, P=0.020) have worse prognosis. The co-expression of BCL6 - and BCL2 S+ has significant influence on prognosis of DLBCL ( P=0.005 and P<0.001) , in which BCL6 +/non-BCL2 S+ ( n=86) has the best prognosis[3-year-OS (71.6±4.9) %, 3-year-PFS (67.0±5.1) %], and BCL6 -/BCL2 S+ ( n=10) has the worst prognosis[3-year-OS (20.0±12.6) %, 3-year-PFS (10.0±9.5) %]; the co-expression of BCL6 - and P53 + has no significant influence on prognosis ( P=0.061 and P=0.089) , however, those cases with BCL6 +/P53 - ( n=98) often get better prognosis[3-year-OS (70.6±4.7) %, 3-year-PFS (64.6±4.9) %] than others; the co-expression of P53 + and BCL2 S+ has significant influence on prognosis of DLBCL ( P<0.001 and P<0.001) , and P53 +/BCL2 S+ ( n=5) has the worst prognosis (3-year-OS and 3-year-PFS are both 0) ; BCL2 S+ cases get shorter OS and PFS, regardless of the expression of BCL6 and P53. Conclusion:The expression and co-expression of BCL6 negative, P53 positive and BCL2 S+ have certain value in the prognostic evaluation of DLBCL, especially in the group of age≤60-year-old and IPI score 0-2.

Objective: To investigate the strong expression (S+) of P53 and BCL2 proteins in MYC/BCL2 double-expression DLBCL (DEL) and whether they can be used for the prognostic evaluation and stratified diagnosis of DELs. Methods: Tissue microarray were made by filed FFPE blocks of 174 DLBCL cases. The translocation of MYC, BCL2 and BCL6 genes were detected by FISH, and the proteins were detected by IHC. Data of clinicopathologic features and follow up of patients were collected and OS (overall survival) and PFS (progression free survival) were analyzed by statistics. Results: Eight double-hit lymphomas (DHLs) were identified in all cases, and 45 DELs were selected from 166 remaining cases, which have no significant difference in OS and PFS compared with non-DEL cases (P=0.668 and P=0.790) . Of 42 DEL-cases with follow up data, 24 cases with P53+ or/and BCL2 (S+) are significantly shorter OS and PFS than others (P=0.003 and P=0.000) , in which the cases with P53+/BCL2 (S+) co-expression were the worst prognosis, and P53/BCL2 co-weaker positive DEL cases even have superior OS and PFS than those non-DELs. Although statistics showed that the cases of P53+ or/and BCL2 (S+) have a lower OS and PFS in total cases (P=0.063 and P=0.024) , it is not the case when the DEL-cases take out from total cases, that is the cases with P53+ or/and BCL2 (S+) are as similar OS and PFS as others in non-DEL group (P=0.590 and P=0.550) . Conclusion The strong expression of P53 and BCL2 proteins can be used as indicators of stratified diagnosis and poor prognosis of DEL.

The immune checkpoint inhibitors (ICI) represented by programmed death 1/programmed death ligand 1 (PD-1/PD-L1) antibody opened a new era of immunotherapy. However, PD-1/PD-L1 inhibitors have not been approved for indications in the field of malignant lymphoma except for classic Hodgkin lymphoma (cHL) and primary mediastinal large B-cell lymphoma. Researchers have actively explored different lymphoma subtypes with single drugs or combined therapy, and achieved certain effect initially. The latest advances of ICI in cHL, B-cell non-Hodgkin lymphoma and T-cell lymphoma and the management of immune-related adverse events are briefly introduced in this paper.

PD-1/PD-L1 (programmed cell death 1/programmed cell death 1 ligand 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) are currently approved major immune checkpoints. Immune checkpoint inhibitors against them are novel monoclonal antibodies that perform well in a variety of malignancies such as melanoma, renal cell carcinoma, non-small-cell lung cancer, urothelial carcinoma and Hodgkin′s lymphoma. However, with the increasing use of immune checkpoint inhibitors, immune-related adverse events cannot be ignored. The incidence of gastrointestinal toxicity is second only to skin toxicity. In this review, we focused on the mechanisms of these immune checkpoint inhibitors and the characteristics of gastrointestinal toxicity induced by them, and also discussed the clinical management strategies.

Chimeric antigen receptor T-cell (CAR-T) is one of the effective methods for treatment of lymphoma. The way to improve the efficacy and control the reverse reactions still needs to be explored further. Several clinical trials have indicated CAR-T could have favorable effects on the B-cell lymphoma patients with controllable reverse reactions. However, antigen loss is a major factor for the acquired resistance to CD19 CAR-T therapy. Other clinical researches, including CD22 for treatment of B-cell lymphoma and CD30 for Hodgkin lymphoma, have increased the efficacy of CAR-T. Moreover, lots of trials have suggested that the patients who received cyclophosphamide or bendamustine plus fludarabine lymphodepletion can get a high effective rate.

Objective:To detect Bruton tyrosin kinase (BTK) expression in patients with mantle cell lymphoma (MCL) and analyze its correlation with clinical features and prognosis. Methods:A total of 32 cases of MCL tissues and 10 cases of benign lymph nodes were sampled and stained with immunohistochemical (IHC) staining. Clinical data of these patients were analyzed using SPSS 17.0. Results:BTK was positively expressed in MCL and normal lymphoid tissues and was more strongly expressed in MCL tissue than in normal lym-phoid tissue. Moreover, BTK expression level was correlated with Ki-67 and MIPI scores. Prognosis analysis showed that patients with high BTK expression exhibited shorter progression-free survival (PFS) than patients with low expression levels (P=0.030);however, no significant difference in overall survival (OS) was observed (P=0.073). Single-factor analysis of PFS showed that age≥65 years, ECOG score≥2, bone marrow involvement, strongly positive BTK expression, Ki-67>30%, and MIPI score≥6 are poor prognostic factors for patients with MCL. Only MIPI score≥6 is considered an independent poor prognostic factor in the multivariate analysis. Conclusion:BTK is strongly and positively expressed in patients with MCL, and its expression level is correlated with Ki-67 and MIPI scores. Patients with high-level BTK expression usually exhibit shorter PFS than those with low-level BTK expression;however, owing to short follow-up time and limited sample size, high-level BTK expression cannot be considered an independent poor prognostic factor for PFS.

Cancer immunotherapy uses the host′s immune system to mobilize immune cells to rec-ognize and eventually eliminate cancer cells .At present, studies in terms of cancer immunotherapy mainly focus on programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) antibody, cytotoxic T-lymphocyte-associated protein 4 ( CTLA-4 ) antibody, chimeric antigen receptor T-cell immunotherapy (CAR-T), T cell receptor Immunotherapy (TCR-T), etc.Despite the fact that cancer immunotherapies elicit unprecedented durable responses in clinical therapy , they appear to be ineffective to some patients .In addition, some responders relapse and show resistance to immunotherapies even if their symptoms are re -lieved for a time .Resistance to cancer immunotherapy can be categorized into primary , adaptive and ac-quired, which can occur in every stage during the process of anti-tumor response.In this review, we discuss the known mechanisms of resistance and provide a rationale for the use of combination therapy to overcome resistance.

Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL) is a rare and distinct variant of DLBCL. It is classified as a unique subtype of DLBCL in the 2008 WHO classification of lymphomas. No standard and effective therapeutic regi-men is available for ALK+DLBCL because it shows a more aggressive clinical course and frequent relapse. Therefore, a standardized and individualized treatment is needed to benefit more patients diagnosed with ALK+DLBCL through a multiple disciplinary team. This arti-cle presents a case of an ALK+DLBCL patient who relapsed after transplantation and was successfully treated with the ALK kinase inhibi-tor Crizotinib.

The human immune system has the regulatory functions of eradicating pathogens and limiting excessive inflammation, which protect the surrounding tissue from being damaged. The immune bal-ance of self-limiting is mainly controlled by complex interactions between antigen-presenting cells ( APCs ) and T cells. However, the immune balance is destroyed in cancer, which results in immune evasion and tumor metastasis or promotes the development of drug resistance. Immune checkpoints play critical roles in the immune system. Therefore, blocking tumor immune evasion by targeting the immune checkpoints has be-come a research focus in the treatment of relapsed or refractory malignant tumors. Currently, in the studies of malignant lymphomas, some phaseⅠ/Ⅱclinical studies of immune checkpoint inhibitors have achieved sur-prising results. This review will discuss the regulation and immunotherapy of immune checkpoints in malig-nant lymphomas.