IP Library Granted Patent US 9,945,861
Granted Patent B2
US 9,945,861 · App. 14/372,757 · Granted Apr 17, 2018

Methods for predicting the survival time of a patient suffering from a solid cancer based on density of B cells

Inventors: Jerome Galon (Paris, FR); Franck Pages (Paris, FR); Bernhard Mlecnik (Paris, FR); Gabriela Bindea (Paris, FR); Herve Fridman (Paris, FR)
Assignees: INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE; UNIVERSITE PARIS DESCARTES; ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS (APHP)
G01N33/574G01N2333/7051G01N2333/70517G01N2333/70589G01N2333/70596G01N2800/52
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Quick Facts
Patent No.
US 9,945,861
App. No.
14/372,757
Granted
Apr 17, 2018
Kind
B2
Abstract

The present invention relates to a method for predicting the survival time of a patient suffering from a solid cancer comprising the steps consisting of i) determining the density of B cells at the invasive margin of the tumor (im) in a tumor tissue sample obtained from said patient, ii) comparing said density with a predetermined reference value and iii) providing a good prognosis when the density of B cells at the invasive margin of the tumor is higher than the predetermined reference value and a poor prognosis when the density of B cells at the invasive margin of the tumor is lower than the predetermined reference value.

Claims (83)

1. A method for predicting the survival time of and treating a patient suffering from a solid cancer comprising the steps of:

determining a density of CD20+ B cells at an invasive margin of a tumor (im) in a tumor tissue sample obtained from said patient;

determining a density of one other cell type selected from CD8+ cytotoxic T cells or CD45RO+ memory T cells at the invasive margin of the tumor (im) and at a center of the tumor (ct), wherein the determining steps may be performed with the same or a different tumor tissue sample obtained from said patient;

comparing each density determined in said determining steps with a predetermined reference value;

providing:

a) a good prognosis when:

a1) the density of CD20+ B cells at the invasive margin of the tumor is higher than the predetermined reference value;

a2) the density of said one other cell type at the invasive margin of the tumor (im) is higher than the predetermined reference value; and

a3) the density of said one other cell type at the center of the tumor (ct) is higher than the predetermined reference value;

b) an intermediate prognosis when:

b1) the density of CD20+ B cells at the invasive margin of the tumor is higher than the predetermined reference value;

b2) the density of said one other cell type at the invasive margin of the tumor (im) is lower than the predetermined reference value; and

b3) the density of said one other cell type at the center of the tumor (ct) is higher than the predetermined reference value;

or

b'1) the density of CD20+ B cells at the invasive margin of the tumor is higher than the predetermined reference value;

b'2) the density of said one other cell type at the invasive margin of the tumor (im) is higher than the predetermined reference value; and

b'3) the density of said one other cell type at the center of the tumor (ct) is lower than the predetermined reference value;

or

b''1) the density of CD20+ B cells at the invasive margin of the tumor is lower than the predetermined reference value

b''2) the density of said one other cell type at the invasive margin of the tumor (im) is higher than the predetermined reference value; and

b''3) the density of said one other cell type at the center of the tumor (ct) is higher than the predetermined reference value;

or

bi) the density of CD20+ B cells at the invasive margin of the tumor is higher than the predetermined reference value

bii) the density of said one other cell type at the invasive margin of the tumor (im) is lower than the predetermined reference value; and

biii) the density of said one other cell type at the center of the tumor (ct) is lower than the predetermined reference value;

or

b'i) the density of CD20+ B cells at the invasive margin of the tumor is lower than the predetermined reference value

b'ii) the density of said one other cell type at the invasive margin of the tumor (im) is lower than the predetermined reference value; and

b'iii) the density of said one other cell type at the center of the tumor (ct) is higher than the predetermined reference value;

or

b''i) the density of CD20+ B cells at the invasive margin of the tumor is lower than the predetermined reference value

b''ii) the density of said one other cell type at the invasive margin of the tumor (im) is higher than the predetermined reference value; and

b''iii) the density of said one other cell type at the center of the tumor (ct) is lower than the predetermined reference value; or

c) a poor prognosis when:

c1) the density of CD20+ B cells at the invasive margin of the tumor is lower than the predetermined reference value;

c2) the density of said one other cell type at the invasive margin of the tumor (im) is lower than the predetermined reference value; and

c3) the density of said one other cell type at the center of the tumor (ct) is lower than the predetermined reference value;

and

treating the patient with an appropriate anticancer treatment.

2. The method according to claim 1 , wherein said one other cell type consists in CD8+ cytotoxic cells.

3. The method according to claim 1 , wherein said one other cell type consists in CD45RO memory T cells.

4. The method according to claim 1 , wherein said solid cancer is colorectal cancer.

5. A method for predicting the survival time of and treating a patient suffering from colorectal cancer comprising the steps of i) determining a density of CD20+ B cells at an invasive margin of a tumor (im) in a tumor tissue sample obtained from said patient, ii) comparing said density with a predetermined reference value, iii) providing a good prognosis when the density of B cells at the invasive margin of the tumor is higher than the predetermined reference value and a poor prognosis when the density of B cells at the invasive margin of the tumor is lower than the predetermined reference value; and iv) treating the patient with an anticancer treatment.

6. The method of claim 1 , wherein the solid cancer is not melanoma.

7. A method for predicting the survival time of and treating a patient suffering from colorectal cancer comprising the steps of:

determining a density of CD20+ B cells at an invasive margin of a tumor (im) in a tumor tissue sample obtained from said patient;

determining a density of one other cell type selected from CD8+ cytotoxic T cells or CD45RO+ memory T cells at the invasive margin of the tumor (im) and at a center of the tumor (ct), wherein the determining steps may be performed with the same or a different tumor tissue sample obtained from said patient;

comparing each density determined in said determining steps with a predetermined reference value;

providing:

a) a good prognosis when:

a1) the density of CD20+ B cells at the invasive margin of the tumor is higher than the predetermined reference value;

a2) the density of said one other cell type at the invasive margin of the tumor (im) is higher than the predetermined reference value; and

a3) the density of said one other cell type at the center of the tumor (ct) is higher than the predetermined reference value;

b) an intermediate prognosis when:

b1) the density of CD20+ B cells at the invasive margin of the tumor is higher than the predetermined reference value;

b2) the density of said one other cell type at the invasive margin of the tumor (im) is lower than the predetermined reference value; and

b3) the density of said one other cell type at the center of the tumor (ct) is higher than the predetermined reference value;

or

b'1) the density of CD20+ B cells at the invasive margin of the tumor is higher than the predetermined reference value;

b'2) the density of said one other cell type at the invasive margin of the tumor (im) is higher than the predetermined reference value; and

b'3) the density of said one other cell type at the center of the tumor (ct) is lower than the predetermined reference value;

or

b''1) the density of CD20+ B cells at the invasive margin of the tumor is lower than the predetermined reference value

b''2) the density of said one other cell type at the invasive margin of the tumor (im) is higher than the predetermined reference value; and

b''3) the density of said one other cell type at the center of the tumor (ct) is higher than the predetermined reference value;

or

bi) the density of CD20+ B cells at the invasive margin of the tumor is higher than the predetermined reference value

bii) the density of said one other cell type at the invasive margin of the tumor (im) is lower than the predetermined reference value; and

biii) the density of said one other cell type at the center of the tumor (ct) is lower than the predetermined reference value;

or

b'i) the density of CD20+ B cells at the invasive margin of the tumor is lower than the predetermined reference value

b'ii) the density of said one other cell type at the invasive margin of the tumor (im) is lower than the predetermined reference value; and

b'iii) the density of said one other cell type at the center of the tumor (ct) is higher than the predetermined reference value;

or

b''i) the density of CD20+ B cells at the invasive margin of the tumor is lower than the predetermined reference value

b''ii) the density of said one other cell type at the invasive margin of the tumor (im) is higher than the predetermined reference value; and

b''iii) the density of said one other cell type at the center of the tumor (ct) is lower than the predetermined reference value; or

c) a poor prognosis when:

c1) the density of CD20+ B cells at the invasive margin of the tumor is lower than the predetermined reference value;

c2) the density of said one other cell type at the invasive margin of the tumor (im) is lower than the predetermined reference value; and

c3) the density of said one other cell type at the center of the tumor (ct) is lower than the predetermined reference value;

and

treating the patient with an appropriate anticancer treatment.

Assignments (5)
CHANGE OF NAME Recorded Mar 25, 2022
From: UNIVERSITÉ DE PARIS
To: UNIVERSITÉ PARIS CITÉ
Reel/Frame 059504/0225 →
MERGER Recorded Jul 22, 2021
From: UNIVERSITE DE PARIS DESCARTES
To: UNIVERSITE DE PARIS
Reel/Frame 056958/0603 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 21, 2015
From: UNIVERSITE PIERRE ET MARIE CURIE - PARIS 6
To: INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE); UNIVERSITE PARIS DESCARTES; ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS (APHP)
Reel/Frame 036140/0320 →
CORRECTIVE ASSIGNMENT TO CORRECT THE OMITTED FOURTH ASSIGNEE PREVIOUSLY RECORDED AT REEL: 034675 FRAME: 0068. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded Jan 13, 2015
From: GALON, JEROME; PAGES, FRANCK; MLECNIK, BERNHARD; BINDEA, GABRIELA; FRIDMAN, HERVE
To: INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE); UNIVERSITE PARIS DESCARTES; ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS (APHP); UNIVERSITE PIERRE ET MARIE CURIE - PARIS VI
Reel/Frame 034757/0937 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 9, 2015
From: GALON, JEROME; PAGES, FRANCK; MLECNIK, BERNHARD; BINDEA, GABRIELA; FRIDMAN, HERVE
To: INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE); UNIVERSITE PARIS DESCARTES; ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS (APHP)
Reel/Frame 034675/0068 →
Priority Claims (1)
EP 12305072 · Jan 20, 2012 · regional
Continuity (2)
Provisional Application 61600752 · Feb 20, 2012
Related Publication 20140363472A1 · Dec 11, 2014